Pigmentation Disorders

To the Editor:

Segmental vitiligo (SV) accounts for a minority of vitiligo cases and most frequently occurs in children.¹ It characteristically manifests unilaterally and affects a single body area with a sharp midline demarcation. In contrast to nonsegmental vitiligo (NSV), SV typically stabilizes early in the disease progression.¹ The pathophysiology of this vitiligo subtype is not well established, but possible autoinflammatory mechanisms associated with somatic mosaicism, neuronal mechanisms, and/or microvascular skin-homing have been proposed.² We present the case of a pediatric patient with segmental vitiligo of the right hemiface treated with a combination of a topical calcineurin inhibitor and narrow-band UVB (NB-UVB) phototherapy.

An otherwise healthy 7-year-old boy presented to the dermatology department for evaluation of depigmented macules and patches affecting the right hemiface (temporal, periorbital, malar, perioral, preauricular, and mandibular regions) and neck associated with homolateral leukotrichia of the scalp and facial hair as well as the eyelashes of 5 years’ duration. The findings were consistent with SV (Figure 1). The patient previously had been diagnosed based on the clinical findings and treated with continuous application of topical calcineurin inhibitors plus oral cyclosporine (3 mg/kg/d) for 1 year, but the response was poor. The condition had a severe impact on the patient’s quality of life and social relationships. Therapeutic options were discussed with the patient’s caregivers, and ultimately NB-UVB phototherapy was started twice weekly with 10% increases in the dose at each treatment. Topical tacrolimus ointment (1 mg/g) also was started, and the cyclosporine was stopped. Evaluation of treatment progress occurred every 3 months, with progressive repigmentation of the patches following a perifollicular pattern. After 6 months of phototherapy, there was notable repigmentation of the affected areas, particularly in the malar, perioral, and perinasal regions (Figure 2) and the therapeutic response improved after 1 year of treatment (Figure 3). No adverse events were noted during the treatment period.

Segmental vitiligo lacks consistently effective treatment options. This subtype of vitiligo is classically resistant to conventional therapeutic options. Surgery may be a more effective and long-lasting treatment option but is not suitable for every patient.^1,3 Janus kinase (JAK) inhibitors are the newest treatment options being explored for topical and systemic treatment of vitiligo, with promising results in active and stable NSV lesions^4,5; however, SV rarely is represented in case reports and clinical trials. The topical JAK inhibitor ruxolitinib has been approved for use in NSV,⁵ and a phase 2 trial with oral ritlecitinib only included patients with NSV.⁴ Furthermore, JAK inhibitors have been studied and approved for children aged 12 years or older as well as for adults,^4,5 but younger age groups (4-10 years)—in whom SV most frequently manifests, as in our patient—have been excluded from these studies.¹ We present a novel case of SV of the right hemiface in a child that was successfully treated with NB-UVB phototherapy in association with topical calcineurin inhibitors.

The role of phototherapy for the treatment of vitiligo has been well documented, and it frequently is combined with other therapeutic modalities, such as topical anti-inflammatory drugs or, most recently, laser and micrografting techniques.^6,7 The most frequently used modality is NB-UVB. In the active phase, it performs an immunomodulatory role, while in the stable phase, it stimulates migration and activity of perilesional and hair follicle melanocytes.⁸ Initiating therapy early is advisable, particularly during the first 6 months of progression, as there is a higher probability of response^1,3,8; nevertheless, a good response was achieved despite the 5-year evolution of vitiligo in our patient. This is a safe option for a skin condition that may begin early in life and require long-term treatment.⁸ A main concern would be an increased risk for skin cancer associated with repeated NB-UVB exposure, which has not been verified in a recent analysis.⁹

Segmental vitiligo can considerably impact the patient’s quality of life, affecting social interactions and self-perception, particularly in younger patients with facial involvement; thus, effective and safe therapeutic strategies adapted to the individual and their vitiligo lesions should be discussed. Classical treatment options remain valid and provide good results for some patients; therefore, they should not be disregarded even with the rise of innovative therapies.

To the Editor:

Segmental vitiligo (SV) accounts for a minority of vitiligo cases and most frequently occurs in children.¹ It characteristically manifests unilaterally and affects a single body area with a sharp midline demarcation. In contrast to nonsegmental vitiligo (NSV), SV typically stabilizes early in the disease progression.¹ The pathophysiology of this vitiligo subtype is not well established, but possible autoinflammatory mechanisms associated with somatic mosaicism, neuronal mechanisms, and/or microvascular skin-homing have been proposed.² We present the case of a pediatric patient with segmental vitiligo of the right hemiface treated with a combination of a topical calcineurin inhibitor and narrow-band UVB (NB-UVB) phototherapy.

An otherwise healthy 7-year-old boy presented to the dermatology department for evaluation of depigmented macules and patches affecting the right hemiface (temporal, periorbital, malar, perioral, preauricular, and mandibular regions) and neck associated with homolateral leukotrichia of the scalp and facial hair as well as the eyelashes of 5 years’ duration. The findings were consistent with SV (Figure 1). The patient previously had been diagnosed based on the clinical findings and treated with continuous application of topical calcineurin inhibitors plus oral cyclosporine (3 mg/kg/d) for 1 year, but the response was poor. The condition had a severe impact on the patient’s quality of life and social relationships. Therapeutic options were discussed with the patient’s caregivers, and ultimately NB-UVB phototherapy was started twice weekly with 10% increases in the dose at each treatment. Topical tacrolimus ointment (1 mg/g) also was started, and the cyclosporine was stopped. Evaluation of treatment progress occurred every 3 months, with progressive repigmentation of the patches following a perifollicular pattern. After 6 months of phototherapy, there was notable repigmentation of the affected areas, particularly in the malar, perioral, and perinasal regions (Figure 2) and the therapeutic response improved after 1 year of treatment (Figure 3). No adverse events were noted during the treatment period.

Segmental vitiligo lacks consistently effective treatment options. This subtype of vitiligo is classically resistant to conventional therapeutic options. Surgery may be a more effective and long-lasting treatment option but is not suitable for every patient.^1,3 Janus kinase (JAK) inhibitors are the newest treatment options being explored for topical and systemic treatment of vitiligo, with promising results in active and stable NSV lesions^4,5; however, SV rarely is represented in case reports and clinical trials. The topical JAK inhibitor ruxolitinib has been approved for use in NSV,⁵ and a phase 2 trial with oral ritlecitinib only included patients with NSV.⁴ Furthermore, JAK inhibitors have been studied and approved for children aged 12 years or older as well as for adults,^4,5 but younger age groups (4-10 years)—in whom SV most frequently manifests, as in our patient—have been excluded from these studies.¹ We present a novel case of SV of the right hemiface in a child that was successfully treated with NB-UVB phototherapy in association with topical calcineurin inhibitors.

The role of phototherapy for the treatment of vitiligo has been well documented, and it frequently is combined with other therapeutic modalities, such as topical anti-inflammatory drugs or, most recently, laser and micrografting techniques.^6,7 The most frequently used modality is NB-UVB. In the active phase, it performs an immunomodulatory role, while in the stable phase, it stimulates migration and activity of perilesional and hair follicle melanocytes.⁸ Initiating therapy early is advisable, particularly during the first 6 months of progression, as there is a higher probability of response^1,3,8; nevertheless, a good response was achieved despite the 5-year evolution of vitiligo in our patient. This is a safe option for a skin condition that may begin early in life and require long-term treatment.⁸ A main concern would be an increased risk for skin cancer associated with repeated NB-UVB exposure, which has not been verified in a recent analysis.⁹

Segmental vitiligo can considerably impact the patient’s quality of life, affecting social interactions and self-perception, particularly in younger patients with facial involvement; thus, effective and safe therapeutic strategies adapted to the individual and their vitiligo lesions should be discussed. Classical treatment options remain valid and provide good results for some patients; therefore, they should not be disregarded even with the rise of innovative therapies.

To the Editor:

Segmental vitiligo (SV) accounts for a minority of vitiligo cases and most frequently occurs in children.¹ It characteristically manifests unilaterally and affects a single body area with a sharp midline demarcation. In contrast to nonsegmental vitiligo (NSV), SV typically stabilizes early in the disease progression.¹ The pathophysiology of this vitiligo subtype is not well established, but possible autoinflammatory mechanisms associated with somatic mosaicism, neuronal mechanisms, and/or microvascular skin-homing have been proposed.² We present the case of a pediatric patient with segmental vitiligo of the right hemiface treated with a combination of a topical calcineurin inhibitor and narrow-band UVB (NB-UVB) phototherapy.

An otherwise healthy 7-year-old boy presented to the dermatology department for evaluation of depigmented macules and patches affecting the right hemiface (temporal, periorbital, malar, perioral, preauricular, and mandibular regions) and neck associated with homolateral leukotrichia of the scalp and facial hair as well as the eyelashes of 5 years’ duration. The findings were consistent with SV (Figure 1). The patient previously had been diagnosed based on the clinical findings and treated with continuous application of topical calcineurin inhibitors plus oral cyclosporine (3 mg/kg/d) for 1 year, but the response was poor. The condition had a severe impact on the patient’s quality of life and social relationships. Therapeutic options were discussed with the patient’s caregivers, and ultimately NB-UVB phototherapy was started twice weekly with 10% increases in the dose at each treatment. Topical tacrolimus ointment (1 mg/g) also was started, and the cyclosporine was stopped. Evaluation of treatment progress occurred every 3 months, with progressive repigmentation of the patches following a perifollicular pattern. After 6 months of phototherapy, there was notable repigmentation of the affected areas, particularly in the malar, perioral, and perinasal regions (Figure 2) and the therapeutic response improved after 1 year of treatment (Figure 3). No adverse events were noted during the treatment period.

Segmental vitiligo lacks consistently effective treatment options. This subtype of vitiligo is classically resistant to conventional therapeutic options. Surgery may be a more effective and long-lasting treatment option but is not suitable for every patient.^1,3 Janus kinase (JAK) inhibitors are the newest treatment options being explored for topical and systemic treatment of vitiligo, with promising results in active and stable NSV lesions^4,5; however, SV rarely is represented in case reports and clinical trials. The topical JAK inhibitor ruxolitinib has been approved for use in NSV,⁵ and a phase 2 trial with oral ritlecitinib only included patients with NSV.⁴ Furthermore, JAK inhibitors have been studied and approved for children aged 12 years or older as well as for adults,^4,5 but younger age groups (4-10 years)—in whom SV most frequently manifests, as in our patient—have been excluded from these studies.¹ We present a novel case of SV of the right hemiface in a child that was successfully treated with NB-UVB phototherapy in association with topical calcineurin inhibitors.

The role of phototherapy for the treatment of vitiligo has been well documented, and it frequently is combined with other therapeutic modalities, such as topical anti-inflammatory drugs or, most recently, laser and micrografting techniques.^6,7 The most frequently used modality is NB-UVB. In the active phase, it performs an immunomodulatory role, while in the stable phase, it stimulates migration and activity of perilesional and hair follicle melanocytes.⁸ Initiating therapy early is advisable, particularly during the first 6 months of progression, as there is a higher probability of response^1,3,8; nevertheless, a good response was achieved despite the 5-year evolution of vitiligo in our patient. This is a safe option for a skin condition that may begin early in life and require long-term treatment.⁸ A main concern would be an increased risk for skin cancer associated with repeated NB-UVB exposure, which has not been verified in a recent analysis.⁹

Segmental vitiligo can considerably impact the patient’s quality of life, affecting social interactions and self-perception, particularly in younger patients with facial involvement; thus, effective and safe therapeutic strategies adapted to the individual and their vitiligo lesions should be discussed. Classical treatment options remain valid and provide good results for some patients; therefore, they should not be disregarded even with the rise of innovative therapies.

THE DIAGNOSIS: Pigmented Bowen Disease

Histopathology revealed atypical keratinocytes throughout the entire thickness of a pigmented epidermis extending from the basal layer (Figure). Diffuse epidermal hyperpigmentation and melanophages in the papillary dermis were present. There was no dermal invasion or atypical melanocytic proliferation. On dermoscopy, this lesion had small brown globules, smudging, and an asymmetric nonspecific homogeneous pattern. Based on these features as well as the clinical findings, a diagnosis of pigmented Bowen disease (PBD), a rare subtype of squamous cell carcinoma in situ, was made. Complete removal of the lesion was achieved via the biopsy, and the patient was counselled regarding the malignant but noninvasive nature of the lesion. Appropriate follow-up was recommended to monitor for recurrence.

Our case presentation of PBD on the right upper arm in a female patient with a light skin tone is not classic, as PBD lesions usually manifest as well-demarcated scaly plaques on sun-protected sites in men with darker skin tones who are in the sixth to seventh decades of life.¹

Dermoscopy of PBD in patients with lighter skin tones can present diagnostic challenges because characteristic clustered glomerular vessels may be faint or absent, particularly in small lesions such as this one. In such cases, PBD may instead demonstrate structureless brown pigmentation and irregular globules, patterns that overlap with pigmented actinic keratosis (PAK) and melanoma.³

Our case underscores the importance of maintaining a broad differential when evaluating small pigmented macules and reinforces biopsy as the diagnostic gold standard for PBD when dermoscopic findings are nonspecific.

THE DIAGNOSIS: Pigmented Bowen Disease

Histopathology revealed atypical keratinocytes throughout the entire thickness of a pigmented epidermis extending from the basal layer (Figure). Diffuse epidermal hyperpigmentation and melanophages in the papillary dermis were present. There was no dermal invasion or atypical melanocytic proliferation. On dermoscopy, this lesion had small brown globules, smudging, and an asymmetric nonspecific homogeneous pattern. Based on these features as well as the clinical findings, a diagnosis of pigmented Bowen disease (PBD), a rare subtype of squamous cell carcinoma in situ, was made. Complete removal of the lesion was achieved via the biopsy, and the patient was counselled regarding the malignant but noninvasive nature of the lesion. Appropriate follow-up was recommended to monitor for recurrence.

Our case presentation of PBD on the right upper arm in a female patient with a light skin tone is not classic, as PBD lesions usually manifest as well-demarcated scaly plaques on sun-protected sites in men with darker skin tones who are in the sixth to seventh decades of life.¹

Dermoscopy of PBD in patients with lighter skin tones can present diagnostic challenges because characteristic clustered glomerular vessels may be faint or absent, particularly in small lesions such as this one. In such cases, PBD may instead demonstrate structureless brown pigmentation and irregular globules, patterns that overlap with pigmented actinic keratosis (PAK) and melanoma.³

Our case underscores the importance of maintaining a broad differential when evaluating small pigmented macules and reinforces biopsy as the diagnostic gold standard for PBD when dermoscopic findings are nonspecific.

THE DIAGNOSIS: Pigmented Bowen Disease

Histopathology revealed atypical keratinocytes throughout the entire thickness of a pigmented epidermis extending from the basal layer (Figure). Diffuse epidermal hyperpigmentation and melanophages in the papillary dermis were present. There was no dermal invasion or atypical melanocytic proliferation. On dermoscopy, this lesion had small brown globules, smudging, and an asymmetric nonspecific homogeneous pattern. Based on these features as well as the clinical findings, a diagnosis of pigmented Bowen disease (PBD), a rare subtype of squamous cell carcinoma in situ, was made. Complete removal of the lesion was achieved via the biopsy, and the patient was counselled regarding the malignant but noninvasive nature of the lesion. Appropriate follow-up was recommended to monitor for recurrence.

Our case presentation of PBD on the right upper arm in a female patient with a light skin tone is not classic, as PBD lesions usually manifest as well-demarcated scaly plaques on sun-protected sites in men with darker skin tones who are in the sixth to seventh decades of life.¹

Dermoscopy of PBD in patients with lighter skin tones can present diagnostic challenges because characteristic clustered glomerular vessels may be faint or absent, particularly in small lesions such as this one. In such cases, PBD may instead demonstrate structureless brown pigmentation and irregular globules, patterns that overlap with pigmented actinic keratosis (PAK) and melanoma.³

Our case underscores the importance of maintaining a broad differential when evaluating small pigmented macules and reinforces biopsy as the diagnostic gold standard for PBD when dermoscopic findings are nonspecific.

THE DIAGNOSIS: Terra Firma-Forme Dermatosis

During clinical examination, a 70% alcohol swab was utilized to gently rub several of the lesions, which were successfully removed. This confirmed a diagnosis of terra firma-forme dermatosis (TFFD)(also known as Duncan’s dirty dermatosis). The patient’s mother was counseled about the diagnosis and was instructed on how to use alcohol pads to remove the remaining lesions. Three days later, after several treatment sessions at home, the mother reported complete resolution of the lesions with no residual pigmentary changes, ulceration, or scarring (Figures 1 and 2).

Terra firma-forme dermatosis was first described in 1987 in a 12-year-old girl with hyperpigmented plaques on the neck that cleared when rubbing alcohol was applied before biopsy.^1,2 The term terra firma is Latin for “firm land” (or essentially “dirt”) in reference to what often is described as a characteristically “dirty” clinical appearance.² Terra firmaforme dermatosis can manifest anywhere on the body but shows a predilection for the neck, arms and legs, axillae, inguinal region, and umbilicus.³ Lesions typically are described as asymptomatic, smooth, well-circumscribed, reticular papules or patches that are brown or black. Terra firma-forme dermatosis also may demonstrate secondary features such as hyperkeratotic, scaly, velvety, or verrucous plaques and nodules.³

The etiology of this condition is theorized to be a result of abnormal or delayed keratinization and prolonged keratinocyte adhesion.^3,4 There are limited epidemiologic data, but TFFD has shown a predominance in children younger than 18 years (average age of onset, 10 years) with no known predilection for sex or race and no recognized pattern of inheritance.^3-5

Histopathology typically demonstrates epidermal atrophy, hyperkeratosis, and often a component of trapping and compaction of melanin, sebum, microorganisms, and environmental debris.⁵

Management of TFFD is straightforward and generally consists of rubbing with 70% isopropyl alcohol to remove the lesions. For more adherent lesions or for extensive involvement, other keratolytics such as salicylic acid or alpha-hydroxy acids may be used.⁵ For TFFD manifesting in infants and young children, widespread involvement, or lesions involving the face or genitals, a urea-based keratolytic with or without a topical anti-inflammatory is suggested.⁵ Other treatment options include other alpha-hydroxy acids, topical retinoids, and nonpolar solvents such as acetone or CO2 laser for recalcitrant cases.^4,5 Fortunately, most TFFD lesions respond well to conservative therapies, with recurrence reported only in 6.3% (5/79) of patients in one study.³

Dermatosis neglecta is clinically similar to TFFD and often is considered on the same spectrum of disease⁶; however, this entity is associated with decreased bathing or limited hygiene, which could be related to child or elder abuse/neglect or comorbid psychiatric disorders. These conditions can be distinguished by attempting to remove the lesions using soap and water; lesions of dermatosis neglecta will clear, whereas those of TFFD will not.

Metastatic melanoma in pediatric patients has a polymorphous appearance and may or may not be pigmented. Lesions often may be associated with lymphadenopathy of the draining lymph node basins, and nodules and lesions may be firm on palpation.⁷ Linear configurations of metastatic melanoma may represent a satellite or in-transit metastasis. Fortunately, melanoma is extraordinarily rare in children, with an estimated incidence of 2.1 per million for individuals younger than 20 years.⁸

Acanthosis nigricans is characterized by velvety plaques most commonly affecting the posterior neck, axillae, and flexor extremities. These lesions commonly are associated with obesity and insulin resistance but occasionally can be associated with underlying malignancy. In the latter association, acanthosis nigricans lesions tend to manifest more abruptly, often are pruritic, and can involve the mucous membranes. Fortunately, acanthosis nigricans related to malignancy in the pediatric population is rare.⁹

Epidermal nevi may exhibit clinical similarities to TFFD, particularly in lesions with brown/black pigment or with a reticulated or verrucous appearance; however, epidermal nevi often are congenital or manifest within the first few years of life. They commonly are distributed over the lines of Blaschko and have a linear appearance; they also enlarge and thicken as the patient ages.¹⁰

Black-dot tinea capitis, a classic manifestation of endothrix infection, manifests as alopecia with broken hairs and is most commonly caused by Tinea tonsurans.¹¹ The black dots refer to the appearance of the infected hair shafts, which have been weakened and broken off at the follicular ostia. As such, lesions typically are monomorphic and may be interspersed with uninvolved hair shafts. There often is associated scale and a lack of inflammation.^11,12

Additional differential diagnoses to consider include seborrheic keratoses and confluent and reticulated papillomatosis. Further workup (eg, potassium hydroxide preparation of skin scrapings or skin biopsy) may help elucidate the diagnosis.⁵ A simple and cost-effective initial diagnostic tool involves wiping suspicious lesions with a 70% isopropyl alcohol pad to confirm this diagnosis.

THE DIAGNOSIS: Terra Firma-Forme Dermatosis

During clinical examination, a 70% alcohol swab was utilized to gently rub several of the lesions, which were successfully removed. This confirmed a diagnosis of terra firma-forme dermatosis (TFFD)(also known as Duncan’s dirty dermatosis). The patient’s mother was counseled about the diagnosis and was instructed on how to use alcohol pads to remove the remaining lesions. Three days later, after several treatment sessions at home, the mother reported complete resolution of the lesions with no residual pigmentary changes, ulceration, or scarring (Figures 1 and 2).

Terra firma-forme dermatosis was first described in 1987 in a 12-year-old girl with hyperpigmented plaques on the neck that cleared when rubbing alcohol was applied before biopsy.^1,2 The term terra firma is Latin for “firm land” (or essentially “dirt”) in reference to what often is described as a characteristically “dirty” clinical appearance.² Terra firmaforme dermatosis can manifest anywhere on the body but shows a predilection for the neck, arms and legs, axillae, inguinal region, and umbilicus.³ Lesions typically are described as asymptomatic, smooth, well-circumscribed, reticular papules or patches that are brown or black. Terra firma-forme dermatosis also may demonstrate secondary features such as hyperkeratotic, scaly, velvety, or verrucous plaques and nodules.³

The etiology of this condition is theorized to be a result of abnormal or delayed keratinization and prolonged keratinocyte adhesion.^3,4 There are limited epidemiologic data, but TFFD has shown a predominance in children younger than 18 years (average age of onset, 10 years) with no known predilection for sex or race and no recognized pattern of inheritance.^3-5

Histopathology typically demonstrates epidermal atrophy, hyperkeratosis, and often a component of trapping and compaction of melanin, sebum, microorganisms, and environmental debris.⁵

Management of TFFD is straightforward and generally consists of rubbing with 70% isopropyl alcohol to remove the lesions. For more adherent lesions or for extensive involvement, other keratolytics such as salicylic acid or alpha-hydroxy acids may be used.⁵ For TFFD manifesting in infants and young children, widespread involvement, or lesions involving the face or genitals, a urea-based keratolytic with or without a topical anti-inflammatory is suggested.⁵ Other treatment options include other alpha-hydroxy acids, topical retinoids, and nonpolar solvents such as acetone or CO2 laser for recalcitrant cases.^4,5 Fortunately, most TFFD lesions respond well to conservative therapies, with recurrence reported only in 6.3% (5/79) of patients in one study.³

Dermatosis neglecta is clinically similar to TFFD and often is considered on the same spectrum of disease⁶; however, this entity is associated with decreased bathing or limited hygiene, which could be related to child or elder abuse/neglect or comorbid psychiatric disorders. These conditions can be distinguished by attempting to remove the lesions using soap and water; lesions of dermatosis neglecta will clear, whereas those of TFFD will not.

Metastatic melanoma in pediatric patients has a polymorphous appearance and may or may not be pigmented. Lesions often may be associated with lymphadenopathy of the draining lymph node basins, and nodules and lesions may be firm on palpation.⁷ Linear configurations of metastatic melanoma may represent a satellite or in-transit metastasis. Fortunately, melanoma is extraordinarily rare in children, with an estimated incidence of 2.1 per million for individuals younger than 20 years.⁸

Acanthosis nigricans is characterized by velvety plaques most commonly affecting the posterior neck, axillae, and flexor extremities. These lesions commonly are associated with obesity and insulin resistance but occasionally can be associated with underlying malignancy. In the latter association, acanthosis nigricans lesions tend to manifest more abruptly, often are pruritic, and can involve the mucous membranes. Fortunately, acanthosis nigricans related to malignancy in the pediatric population is rare.⁹

Epidermal nevi may exhibit clinical similarities to TFFD, particularly in lesions with brown/black pigment or with a reticulated or verrucous appearance; however, epidermal nevi often are congenital or manifest within the first few years of life. They commonly are distributed over the lines of Blaschko and have a linear appearance; they also enlarge and thicken as the patient ages.¹⁰

Black-dot tinea capitis, a classic manifestation of endothrix infection, manifests as alopecia with broken hairs and is most commonly caused by Tinea tonsurans.¹¹ The black dots refer to the appearance of the infected hair shafts, which have been weakened and broken off at the follicular ostia. As such, lesions typically are monomorphic and may be interspersed with uninvolved hair shafts. There often is associated scale and a lack of inflammation.^11,12

Additional differential diagnoses to consider include seborrheic keratoses and confluent and reticulated papillomatosis. Further workup (eg, potassium hydroxide preparation of skin scrapings or skin biopsy) may help elucidate the diagnosis.⁵ A simple and cost-effective initial diagnostic tool involves wiping suspicious lesions with a 70% isopropyl alcohol pad to confirm this diagnosis.

THE DIAGNOSIS: Terra Firma-Forme Dermatosis

During clinical examination, a 70% alcohol swab was utilized to gently rub several of the lesions, which were successfully removed. This confirmed a diagnosis of terra firma-forme dermatosis (TFFD)(also known as Duncan’s dirty dermatosis). The patient’s mother was counseled about the diagnosis and was instructed on how to use alcohol pads to remove the remaining lesions. Three days later, after several treatment sessions at home, the mother reported complete resolution of the lesions with no residual pigmentary changes, ulceration, or scarring (Figures 1 and 2).

Terra firma-forme dermatosis was first described in 1987 in a 12-year-old girl with hyperpigmented plaques on the neck that cleared when rubbing alcohol was applied before biopsy.^1,2 The term terra firma is Latin for “firm land” (or essentially “dirt”) in reference to what often is described as a characteristically “dirty” clinical appearance.² Terra firmaforme dermatosis can manifest anywhere on the body but shows a predilection for the neck, arms and legs, axillae, inguinal region, and umbilicus.³ Lesions typically are described as asymptomatic, smooth, well-circumscribed, reticular papules or patches that are brown or black. Terra firma-forme dermatosis also may demonstrate secondary features such as hyperkeratotic, scaly, velvety, or verrucous plaques and nodules.³

The etiology of this condition is theorized to be a result of abnormal or delayed keratinization and prolonged keratinocyte adhesion.^3,4 There are limited epidemiologic data, but TFFD has shown a predominance in children younger than 18 years (average age of onset, 10 years) with no known predilection for sex or race and no recognized pattern of inheritance.^3-5

Histopathology typically demonstrates epidermal atrophy, hyperkeratosis, and often a component of trapping and compaction of melanin, sebum, microorganisms, and environmental debris.⁵

Management of TFFD is straightforward and generally consists of rubbing with 70% isopropyl alcohol to remove the lesions. For more adherent lesions or for extensive involvement, other keratolytics such as salicylic acid or alpha-hydroxy acids may be used.⁵ For TFFD manifesting in infants and young children, widespread involvement, or lesions involving the face or genitals, a urea-based keratolytic with or without a topical anti-inflammatory is suggested.⁵ Other treatment options include other alpha-hydroxy acids, topical retinoids, and nonpolar solvents such as acetone or CO2 laser for recalcitrant cases.^4,5 Fortunately, most TFFD lesions respond well to conservative therapies, with recurrence reported only in 6.3% (5/79) of patients in one study.³

Dermatosis neglecta is clinically similar to TFFD and often is considered on the same spectrum of disease⁶; however, this entity is associated with decreased bathing or limited hygiene, which could be related to child or elder abuse/neglect or comorbid psychiatric disorders. These conditions can be distinguished by attempting to remove the lesions using soap and water; lesions of dermatosis neglecta will clear, whereas those of TFFD will not.

Metastatic melanoma in pediatric patients has a polymorphous appearance and may or may not be pigmented. Lesions often may be associated with lymphadenopathy of the draining lymph node basins, and nodules and lesions may be firm on palpation.⁷ Linear configurations of metastatic melanoma may represent a satellite or in-transit metastasis. Fortunately, melanoma is extraordinarily rare in children, with an estimated incidence of 2.1 per million for individuals younger than 20 years.⁸

Acanthosis nigricans is characterized by velvety plaques most commonly affecting the posterior neck, axillae, and flexor extremities. These lesions commonly are associated with obesity and insulin resistance but occasionally can be associated with underlying malignancy. In the latter association, acanthosis nigricans lesions tend to manifest more abruptly, often are pruritic, and can involve the mucous membranes. Fortunately, acanthosis nigricans related to malignancy in the pediatric population is rare.⁹

Epidermal nevi may exhibit clinical similarities to TFFD, particularly in lesions with brown/black pigment or with a reticulated or verrucous appearance; however, epidermal nevi often are congenital or manifest within the first few years of life. They commonly are distributed over the lines of Blaschko and have a linear appearance; they also enlarge and thicken as the patient ages.¹⁰

Black-dot tinea capitis, a classic manifestation of endothrix infection, manifests as alopecia with broken hairs and is most commonly caused by Tinea tonsurans.¹¹ The black dots refer to the appearance of the infected hair shafts, which have been weakened and broken off at the follicular ostia. As such, lesions typically are monomorphic and may be interspersed with uninvolved hair shafts. There often is associated scale and a lack of inflammation.^11,12

Additional differential diagnoses to consider include seborrheic keratoses and confluent and reticulated papillomatosis. Further workup (eg, potassium hydroxide preparation of skin scrapings or skin biopsy) may help elucidate the diagnosis.⁵ A simple and cost-effective initial diagnostic tool involves wiping suspicious lesions with a 70% isopropyl alcohol pad to confirm this diagnosis.

To the Editor:

Millipedes do not have nearly as many feet as their name would suggest; most have fewer than 100.¹ They are not actually insects; they are a wormlike arthropod in the Diplopoda class. Generally these harmless animals can be a welcome resident in gardens because they break down decaying plant material and rejuvenate the soil.¹ However, they are less welcome in the home or underfoot because of what happens when these invertebrates are threatened or crushed.²

Millipedes, which typically have at least 30 pairs of legs, have 2 defense mechanisms: (1) body coiling to withstand external pressure, and (2) secretion of fluids with insecticidal properties from specialized glands distributed along their body.³ These secretions, which are used by the millipede to defend against predators, contain organic compounds including benzoquinone. When these secretions come into contact with skin, pigmentary changes resembling a burn or necrosis and irritation to the skin (pain, burning, itching) occur.^4,5

Millipedes typically are found in tropical and temperate regions worldwide, such as the Amazon rainforest, Southeast Asia, tropical areas of Africa, forests, grasslands, and gardens in North America and Europe.⁶ They also are found in every US state as well as Puerto Rico.¹ Millipedes are nocturnal, favor dark places, and can make their way into residential areas, including homes, basements, gardens, and yards.^2,6 Although millipede burns commonly are reported in tropical regions, we present a case in China.⁶A 33-year-old woman presented with purplish-red discoloration on all 5 toes on the left foot. The patient recounted that she discovered a millipede in her shoe earlier in the day, removed it, and crushed it with her bare foot. That night, while taking a bath, she noticed that the toes had turned purplish-red (Figure 1). The patient brought the crushed millipede with her to the emergency department where she sought treatment. The dermatologist confirmed that it was a millipede; however, the team was unable to determine the specific species because it had been crushed (Figure 2).

Physical examination of the affected toes showed a clear boundary and iodinelike staining. The patient did not report pain. The stained skin had a normal temperature, pulse, texture, and sensation. Dermoscopy revealed multiple black-brown patches on the toes (Figure 3). The pigmented area gradually faded over a 1-month period. Superficial damage to the toenail revealed evidence of black-brown pigmentation on both the nail and the skin underneath. The diagnosis in the dermoscopy report suggested exogenous pigmentation of the toes. The patient was advised that no treatment was needed and that the condition would resolve on its own. At 1-month follow-up, the patient’s toes had returned to their normal color (Figure 4).

The feet are common sites of millipede burns; other exposed areas, such as the arms, face, and eyes, also are potential sites of involvement.⁵ The cutaneous pigmentary changes seen on our patient’s foot were a result of the millipede’s defense mechanism—secreted toxic chemicals that stained the foot. It is important to note that the pigmentation was not associated with the death of the millipede, as the millipede was still alive upon initial contact with the patient’s foot in her shoe. 

When a patient presents with pigmentary changes, several conditions must be ruled out—notably acute arterial thrombosis. Patients with this condition will describe acute pain and weakness in the area of involvement. Physicians inspecting the area will note coldness and pallor in the affected limb as well as a diminished or absent pulse. In severe cases, the skin may exhibit a purplish-red appearance.⁵ Millipede burns also should be distinguished from bacterial endocarditis and cryoglobulinemia.⁷ All 3 conditions can manifest with redness, swelling, blisters, and purpuralike changes. Positive blood culture is an important diagnostic basis for bacterial endocarditis; in addition, routine blood tests will demonstrate a decrease in red blood cells and hemoglobin, and routine urinalysis may show proteinuria and microscopic hematuria. Patients with cryoglobulinemia will have a positive cryoglobulin assay, increased IgM, and often decreased complement.⁷ It also is worth noting that millipede burns might resemble child abuse in pediatric patients, necessitating further evaluation.⁵ 

It is unusual to see a millipede burn in nontropical regions. Therefore, the identification of our patient’s millipede burn was notable and serves as a reminder to keep this diagnosis in the differential when caring for patients with pigmentary changes. An accurate diagnosis hinges on being alert to a millipede exposure history and recognizing the clinical manifestations. For affected patients, it may be beneficial to recommend they advise friends and relatives to avoid skin contact with millipedes and most importantly to avoid stepping on them with bare feet.

To the Editor:

Millipedes do not have nearly as many feet as their name would suggest; most have fewer than 100.¹ They are not actually insects; they are a wormlike arthropod in the Diplopoda class. Generally these harmless animals can be a welcome resident in gardens because they break down decaying plant material and rejuvenate the soil.¹ However, they are less welcome in the home or underfoot because of what happens when these invertebrates are threatened or crushed.²

Millipedes, which typically have at least 30 pairs of legs, have 2 defense mechanisms: (1) body coiling to withstand external pressure, and (2) secretion of fluids with insecticidal properties from specialized glands distributed along their body.³ These secretions, which are used by the millipede to defend against predators, contain organic compounds including benzoquinone. When these secretions come into contact with skin, pigmentary changes resembling a burn or necrosis and irritation to the skin (pain, burning, itching) occur.^4,5

Millipedes typically are found in tropical and temperate regions worldwide, such as the Amazon rainforest, Southeast Asia, tropical areas of Africa, forests, grasslands, and gardens in North America and Europe.⁶ They also are found in every US state as well as Puerto Rico.¹ Millipedes are nocturnal, favor dark places, and can make their way into residential areas, including homes, basements, gardens, and yards.^2,6 Although millipede burns commonly are reported in tropical regions, we present a case in China.⁶A 33-year-old woman presented with purplish-red discoloration on all 5 toes on the left foot. The patient recounted that she discovered a millipede in her shoe earlier in the day, removed it, and crushed it with her bare foot. That night, while taking a bath, she noticed that the toes had turned purplish-red (Figure 1). The patient brought the crushed millipede with her to the emergency department where she sought treatment. The dermatologist confirmed that it was a millipede; however, the team was unable to determine the specific species because it had been crushed (Figure 2).

Physical examination of the affected toes showed a clear boundary and iodinelike staining. The patient did not report pain. The stained skin had a normal temperature, pulse, texture, and sensation. Dermoscopy revealed multiple black-brown patches on the toes (Figure 3). The pigmented area gradually faded over a 1-month period. Superficial damage to the toenail revealed evidence of black-brown pigmentation on both the nail and the skin underneath. The diagnosis in the dermoscopy report suggested exogenous pigmentation of the toes. The patient was advised that no treatment was needed and that the condition would resolve on its own. At 1-month follow-up, the patient’s toes had returned to their normal color (Figure 4).

The feet are common sites of millipede burns; other exposed areas, such as the arms, face, and eyes, also are potential sites of involvement.⁵ The cutaneous pigmentary changes seen on our patient’s foot were a result of the millipede’s defense mechanism—secreted toxic chemicals that stained the foot. It is important to note that the pigmentation was not associated with the death of the millipede, as the millipede was still alive upon initial contact with the patient’s foot in her shoe. 

When a patient presents with pigmentary changes, several conditions must be ruled out—notably acute arterial thrombosis. Patients with this condition will describe acute pain and weakness in the area of involvement. Physicians inspecting the area will note coldness and pallor in the affected limb as well as a diminished or absent pulse. In severe cases, the skin may exhibit a purplish-red appearance.⁵ Millipede burns also should be distinguished from bacterial endocarditis and cryoglobulinemia.⁷ All 3 conditions can manifest with redness, swelling, blisters, and purpuralike changes. Positive blood culture is an important diagnostic basis for bacterial endocarditis; in addition, routine blood tests will demonstrate a decrease in red blood cells and hemoglobin, and routine urinalysis may show proteinuria and microscopic hematuria. Patients with cryoglobulinemia will have a positive cryoglobulin assay, increased IgM, and often decreased complement.⁷ It also is worth noting that millipede burns might resemble child abuse in pediatric patients, necessitating further evaluation.⁵ 

It is unusual to see a millipede burn in nontropical regions. Therefore, the identification of our patient’s millipede burn was notable and serves as a reminder to keep this diagnosis in the differential when caring for patients with pigmentary changes. An accurate diagnosis hinges on being alert to a millipede exposure history and recognizing the clinical manifestations. For affected patients, it may be beneficial to recommend they advise friends and relatives to avoid skin contact with millipedes and most importantly to avoid stepping on them with bare feet.

To the Editor:

Millipedes do not have nearly as many feet as their name would suggest; most have fewer than 100.¹ They are not actually insects; they are a wormlike arthropod in the Diplopoda class. Generally these harmless animals can be a welcome resident in gardens because they break down decaying plant material and rejuvenate the soil.¹ However, they are less welcome in the home or underfoot because of what happens when these invertebrates are threatened or crushed.²

Millipedes, which typically have at least 30 pairs of legs, have 2 defense mechanisms: (1) body coiling to withstand external pressure, and (2) secretion of fluids with insecticidal properties from specialized glands distributed along their body.³ These secretions, which are used by the millipede to defend against predators, contain organic compounds including benzoquinone. When these secretions come into contact with skin, pigmentary changes resembling a burn or necrosis and irritation to the skin (pain, burning, itching) occur.^4,5

Millipedes typically are found in tropical and temperate regions worldwide, such as the Amazon rainforest, Southeast Asia, tropical areas of Africa, forests, grasslands, and gardens in North America and Europe.⁶ They also are found in every US state as well as Puerto Rico.¹ Millipedes are nocturnal, favor dark places, and can make their way into residential areas, including homes, basements, gardens, and yards.^2,6 Although millipede burns commonly are reported in tropical regions, we present a case in China.⁶A 33-year-old woman presented with purplish-red discoloration on all 5 toes on the left foot. The patient recounted that she discovered a millipede in her shoe earlier in the day, removed it, and crushed it with her bare foot. That night, while taking a bath, she noticed that the toes had turned purplish-red (Figure 1). The patient brought the crushed millipede with her to the emergency department where she sought treatment. The dermatologist confirmed that it was a millipede; however, the team was unable to determine the specific species because it had been crushed (Figure 2).

Physical examination of the affected toes showed a clear boundary and iodinelike staining. The patient did not report pain. The stained skin had a normal temperature, pulse, texture, and sensation. Dermoscopy revealed multiple black-brown patches on the toes (Figure 3). The pigmented area gradually faded over a 1-month period. Superficial damage to the toenail revealed evidence of black-brown pigmentation on both the nail and the skin underneath. The diagnosis in the dermoscopy report suggested exogenous pigmentation of the toes. The patient was advised that no treatment was needed and that the condition would resolve on its own. At 1-month follow-up, the patient’s toes had returned to their normal color (Figure 4).

The feet are common sites of millipede burns; other exposed areas, such as the arms, face, and eyes, also are potential sites of involvement.⁵ The cutaneous pigmentary changes seen on our patient’s foot were a result of the millipede’s defense mechanism—secreted toxic chemicals that stained the foot. It is important to note that the pigmentation was not associated with the death of the millipede, as the millipede was still alive upon initial contact with the patient’s foot in her shoe. 

When a patient presents with pigmentary changes, several conditions must be ruled out—notably acute arterial thrombosis. Patients with this condition will describe acute pain and weakness in the area of involvement. Physicians inspecting the area will note coldness and pallor in the affected limb as well as a diminished or absent pulse. In severe cases, the skin may exhibit a purplish-red appearance.⁵ Millipede burns also should be distinguished from bacterial endocarditis and cryoglobulinemia.⁷ All 3 conditions can manifest with redness, swelling, blisters, and purpuralike changes. Positive blood culture is an important diagnostic basis for bacterial endocarditis; in addition, routine blood tests will demonstrate a decrease in red blood cells and hemoglobin, and routine urinalysis may show proteinuria and microscopic hematuria. Patients with cryoglobulinemia will have a positive cryoglobulin assay, increased IgM, and often decreased complement.⁷ It also is worth noting that millipede burns might resemble child abuse in pediatric patients, necessitating further evaluation.⁵ 

It is unusual to see a millipede burn in nontropical regions. Therefore, the identification of our patient’s millipede burn was notable and serves as a reminder to keep this diagnosis in the differential when caring for patients with pigmentary changes. An accurate diagnosis hinges on being alert to a millipede exposure history and recognizing the clinical manifestations. For affected patients, it may be beneficial to recommend they advise friends and relatives to avoid skin contact with millipedes and most importantly to avoid stepping on them with bare feet.

Vitiligo is a common autoimmune disorder characterized by cutaneous depigmentation that has a substantial impact on patient quality of life.¹ Vitiligo affects approximately 28.5 million individuals globally, with the highest lifetime prevalence occurring in Central Europe and South Asia.² In the United States, Asian American and Hispanic/Latine populations most commonly are affected.³ The accompanying psychosocial burdens of vitiligo are particularly substantial among individuals with darker skin types, as evidenced by higher rates of concomitant anxiety and depression in these patients.⁴ Despite this, patients with skin of color are underrepresented in vitiligo research.²

Treatment algorithms developed based on worldwide expert consensus recommendations provide valuable insights into the management of segmental and nonsegmental vitiligo.⁵ The mainstay therapeutics include topical and oral corticosteroids, topical calcineurin inhibitors, and phototherapy. While vitiligo pathogenesis is not completely understood, recent advances have focused on the role of the Janus kinase (JAK)/signal transducer and activator of transcription pathway. Interferon gamma drives vitiligo pathogenesis through this pathway, upregulating C-X-C motif chemokine ligand 10 and promoting CD8+ T-cell recruitment, resulting in targeted melanocyte destruction.⁶ The emergence of targeted therapeutics may address equity and inclusion gaps. Herein, we highlight innovations in vitiligo treatment with a focus on oral and topical JAK inhibitors.

Oral JAK Inhibitors for Vitiligo

The therapeutic potential of JAK inhibitors for vitiligo was first reported when patients with alopecia areata and comorbid vitiligo experienced repigmentation of the skin following administration of oral ruxolitinib.⁷ Since this discovery, other oral JAK inhibitors have been investigated for vitiligo treatment. A phase 2b randomized clinical trial (RCT) of 364 patients examined oral ritlecitinib, a JAK3 inhibitor, and found it to be effective in treating active nonsegmental vitiligo.⁸ Patients aged 18 to 65 years with active nonsegmental vitiligo that had been present for 3 months or more as well as 4% to 50% body surface area (BSA) affected excluding acral surfaces and at least 0.25% facial involvement were included. Treatment groups received 50 mg (with or without a 100- or 200- mg loading dose), 30 mg, or 10 mg daily for 24 weeks. The primary endpoint measured the percentage change in Facial Vitiligo Area Scoring Index (F-VASI) score. Significant differences in F-VASI percentage change compared with placebo occurred for those in the 50-mg group who received a loading dose (-21.2 vs 2.1 [P<.001]) and those who did not receive a loading dose (–18.5 vs 2.1 [P<.001]) as well as the 30-mg group (-14.6 vs 2.1 [P=.01]). Continued repigmentation of the skin was observed in the 24-week extension period, indicating that longer treatment periods may be necessary for optimal repigmentation results. Ritlecitinib generally was well tolerated, and the most common treatment-emergent adverse events were nasopharyngitis (15.9%), upper respiratory tract infection (11.5%), and headache (8.8%). Most patients identified as White (67.6%), with 23.6% identifying as Asian and 2.7% identifying as Black. The authors stated that continued improvement was observed in the extension period across all skin types; however, the data were not reported.⁸

Upadacitnib, an oral selective JAK1 inhibitor, also has demonstrated efficacy in nonsegmental vitiligo in a phase 2 RCT.⁹ Adult patients (N=185) with nonsegmental vitiligo were randomized to receive upadacitinib 6 mg, 11 mg, or 22 mg or placebo (the placebo group subsequently was switched to upadacitinib 11 mg or 22 mg after 24 weeks). The primary endpoint measured the percentage change in F-VASI score at 24 weeks. The higher doses of upadacitinib resulted in significant changes in F-VASI scored compared with placebo (6 mg: -7.60 [95% CI, -22.18 to 6.97][P=.30]; 11 mg: -21.27 [95% CI, -36.02 to -6.52][P=.01]; 22 mg: -19.60 [95% CI, -35.04 to –4.16][P=.01]). As with ritlecitinib, continued repigmentation was observed beyond the initial 24-week period. Of the 185 participants, 5.9% identified as Black and 13.5% identified as Asian. The investigators reported that the percentage change in F-VASI score was consistent across skin types.⁹ The results of these phase 2 RCTs are encouraging, and we anticipate the findings of 2 phase 3 RCTs for ritlecitinib and upadacitinib that currently are underway (Clinicaltrials.gov identifiers NCT05583526 and NCT06118411).

Topical JAK Inhibitors for Vitiligo

Tofacitinib cream 2%, a selective JAK3 inhibitor, has shown therapeutic potential for treatment of vitiligo. One of the earliest pilot studies on topical tofacitinib examined the efficacy of tofacitinib cream 2% applied twice daily combined with narrowband UVB therapy 3 times weekly for facial vitiligo. The investigators reported repigmentation of the skin in all 11 patients (which included 4 Asian patients and 1 Hispanic patient), with a mean improvement of 70% in F-VASI score (range, 50%-87%).¹⁰ In a nonrandomized cohort study of 16 patients later that year, twice-daily application of tofacitinib cream 2% on facial and nonfacial vitiligo lesions resulted in partial repigmentation in 81.3% of patients: 4 (25%) achieved greater than 90% improvement, 5 (31.3%) achieved improvement of 25% to 75%, and 4 (25%) achieved 5% to 15% improvement.¹¹ The researchers also found that tofacitinib cream 2% was significantly more effective in facial than nonfacial lesions (P=.02).

While tofacitinib has shown promise in early studies, recent advancements have led to US Food and Drug Administration approval of ruxolitinib cream 1.5%, another topical JAK inhibitor that has undergone robust clinical testing for vitiligo.^12-14 Ruxolitinib, a JAK1, JAK2, and JAK3 inhibitor, is the first and only US Food and Drug Administration–approved topical JAK inhibitor for vitiligo.^14,15 Two phase 3, double-blind, vehicle-controlled trials of identical design conducted across 101 centers in North America and Europe (TRuE-V1 and TRuE-V2) assessed the efficacy of ruxolitinib cream 1.5% in 674 patients aged 12 years and older with nonsegmental vitiligo covering 10% or lower total BSA.¹³ In both trials, twice-daily application of topical ruxolitinib resulted in greater facial repigmentation and improvement in F-VASI75 score (ie, a reduction of at least 75% from baseline) at 24 weeks in 29.9% (66/221) and 30.1% (69/222) of patients in TRuE-V1 and TRuE-V2, respectively. Continued application through 52 weeks resulted in F-VASI75 response in 52.6% (91/173) and 48.0% (85/177) of patients in TRuE-V1 and TRuE-V2, respectively. The most frequently reported adverse events were acne (6.3% [14/221] and 6.6% [15/228]), nasopharyngitis (5.4% [12/221] and 6.1% [14/228]), and pruritus (5.4% [12/221] and 5.3% [12/228]). These findings align with prior subgroup analyses of an earlier phase 2 double- blind RCT of ruxolitinib cream 1.5% that indicated similar improvement in vitiligo among patients with differing skin tones.¹⁷

There are no additional large-scale RCTs examining topical JAK inhibitors with intentional subanalysis of diverse skin tones.^16,17,18 Studies examining topical JAK inhibitors have expanded to be more inclusive, providing hope for the future of topical vitiligo therapeutics for all patients.

Final Thoughts

It is imperative to increase racial/ethnic and skin type diversity in research on JAK inhibitors for vitiligo. While the studies mentioned here are inclusive of an array of races and skin tones, it is crucial that future research continue to expand the number of diverse participants, especially given the increased psychosocial burdens of vitiligo in patients with darker skin types.⁴ Intentional subgroup analyses across skin tones are vital to characterize and unmask potential differences between lighter and darker skin types. This point was exemplified by a 2024 RCT that investigated ritlecitinib efficacy with biomarker analysis across skin types.¹⁹ For patients receiving ritlecitinib 50 mg, IL-9 and IL-22 expression were decreased in darker vs lighter skin tones (P<.05). This intentional and inclusive analysis revealed a potential immunologic mechanism for why darker skin tones respond to JAK inhibitor therapy earlier than lighter skin tones.¹⁹

In the expanding landscape of oral and topical JAK inhibitors for vitiligo, continued efforts to assess these therapies across a range of skin tones and racial/ ethnic groups are critical. The efficacy of JAK inhibitors in other populations, including pediatric patients and patients with refractory segmental disease, have been reported.^20,21 As larger studies are developed based on the success of individual cases, researchers should investigate the efficacy of JAK inhibitors for various vitiligo subtypes (eg, segmental, nonsegmental) and recalcitrant disease and conduct direct comparisons with traditional treatments across diverse skin tones and racial/ethnic subgroup analyses to ensure broad therapeutic applicability.

Vitiligo is a common autoimmune disorder characterized by cutaneous depigmentation that has a substantial impact on patient quality of life.¹ Vitiligo affects approximately 28.5 million individuals globally, with the highest lifetime prevalence occurring in Central Europe and South Asia.² In the United States, Asian American and Hispanic/Latine populations most commonly are affected.³ The accompanying psychosocial burdens of vitiligo are particularly substantial among individuals with darker skin types, as evidenced by higher rates of concomitant anxiety and depression in these patients.⁴ Despite this, patients with skin of color are underrepresented in vitiligo research.²

Treatment algorithms developed based on worldwide expert consensus recommendations provide valuable insights into the management of segmental and nonsegmental vitiligo.⁵ The mainstay therapeutics include topical and oral corticosteroids, topical calcineurin inhibitors, and phototherapy. While vitiligo pathogenesis is not completely understood, recent advances have focused on the role of the Janus kinase (JAK)/signal transducer and activator of transcription pathway. Interferon gamma drives vitiligo pathogenesis through this pathway, upregulating C-X-C motif chemokine ligand 10 and promoting CD8+ T-cell recruitment, resulting in targeted melanocyte destruction.⁶ The emergence of targeted therapeutics may address equity and inclusion gaps. Herein, we highlight innovations in vitiligo treatment with a focus on oral and topical JAK inhibitors.

Oral JAK Inhibitors for Vitiligo

The therapeutic potential of JAK inhibitors for vitiligo was first reported when patients with alopecia areata and comorbid vitiligo experienced repigmentation of the skin following administration of oral ruxolitinib.⁷ Since this discovery, other oral JAK inhibitors have been investigated for vitiligo treatment. A phase 2b randomized clinical trial (RCT) of 364 patients examined oral ritlecitinib, a JAK3 inhibitor, and found it to be effective in treating active nonsegmental vitiligo.⁸ Patients aged 18 to 65 years with active nonsegmental vitiligo that had been present for 3 months or more as well as 4% to 50% body surface area (BSA) affected excluding acral surfaces and at least 0.25% facial involvement were included. Treatment groups received 50 mg (with or without a 100- or 200- mg loading dose), 30 mg, or 10 mg daily for 24 weeks. The primary endpoint measured the percentage change in Facial Vitiligo Area Scoring Index (F-VASI) score. Significant differences in F-VASI percentage change compared with placebo occurred for those in the 50-mg group who received a loading dose (-21.2 vs 2.1 [P<.001]) and those who did not receive a loading dose (–18.5 vs 2.1 [P<.001]) as well as the 30-mg group (-14.6 vs 2.1 [P=.01]). Continued repigmentation of the skin was observed in the 24-week extension period, indicating that longer treatment periods may be necessary for optimal repigmentation results. Ritlecitinib generally was well tolerated, and the most common treatment-emergent adverse events were nasopharyngitis (15.9%), upper respiratory tract infection (11.5%), and headache (8.8%). Most patients identified as White (67.6%), with 23.6% identifying as Asian and 2.7% identifying as Black. The authors stated that continued improvement was observed in the extension period across all skin types; however, the data were not reported.⁸

Upadacitnib, an oral selective JAK1 inhibitor, also has demonstrated efficacy in nonsegmental vitiligo in a phase 2 RCT.⁹ Adult patients (N=185) with nonsegmental vitiligo were randomized to receive upadacitinib 6 mg, 11 mg, or 22 mg or placebo (the placebo group subsequently was switched to upadacitinib 11 mg or 22 mg after 24 weeks). The primary endpoint measured the percentage change in F-VASI score at 24 weeks. The higher doses of upadacitinib resulted in significant changes in F-VASI scored compared with placebo (6 mg: -7.60 [95% CI, -22.18 to 6.97][P=.30]; 11 mg: -21.27 [95% CI, -36.02 to -6.52][P=.01]; 22 mg: -19.60 [95% CI, -35.04 to –4.16][P=.01]). As with ritlecitinib, continued repigmentation was observed beyond the initial 24-week period. Of the 185 participants, 5.9% identified as Black and 13.5% identified as Asian. The investigators reported that the percentage change in F-VASI score was consistent across skin types.⁹ The results of these phase 2 RCTs are encouraging, and we anticipate the findings of 2 phase 3 RCTs for ritlecitinib and upadacitinib that currently are underway (Clinicaltrials.gov identifiers NCT05583526 and NCT06118411).

Topical JAK Inhibitors for Vitiligo

Tofacitinib cream 2%, a selective JAK3 inhibitor, has shown therapeutic potential for treatment of vitiligo. One of the earliest pilot studies on topical tofacitinib examined the efficacy of tofacitinib cream 2% applied twice daily combined with narrowband UVB therapy 3 times weekly for facial vitiligo. The investigators reported repigmentation of the skin in all 11 patients (which included 4 Asian patients and 1 Hispanic patient), with a mean improvement of 70% in F-VASI score (range, 50%-87%).¹⁰ In a nonrandomized cohort study of 16 patients later that year, twice-daily application of tofacitinib cream 2% on facial and nonfacial vitiligo lesions resulted in partial repigmentation in 81.3% of patients: 4 (25%) achieved greater than 90% improvement, 5 (31.3%) achieved improvement of 25% to 75%, and 4 (25%) achieved 5% to 15% improvement.¹¹ The researchers also found that tofacitinib cream 2% was significantly more effective in facial than nonfacial lesions (P=.02).

While tofacitinib has shown promise in early studies, recent advancements have led to US Food and Drug Administration approval of ruxolitinib cream 1.5%, another topical JAK inhibitor that has undergone robust clinical testing for vitiligo.^12-14 Ruxolitinib, a JAK1, JAK2, and JAK3 inhibitor, is the first and only US Food and Drug Administration–approved topical JAK inhibitor for vitiligo.^14,15 Two phase 3, double-blind, vehicle-controlled trials of identical design conducted across 101 centers in North America and Europe (TRuE-V1 and TRuE-V2) assessed the efficacy of ruxolitinib cream 1.5% in 674 patients aged 12 years and older with nonsegmental vitiligo covering 10% or lower total BSA.¹³ In both trials, twice-daily application of topical ruxolitinib resulted in greater facial repigmentation and improvement in F-VASI75 score (ie, a reduction of at least 75% from baseline) at 24 weeks in 29.9% (66/221) and 30.1% (69/222) of patients in TRuE-V1 and TRuE-V2, respectively. Continued application through 52 weeks resulted in F-VASI75 response in 52.6% (91/173) and 48.0% (85/177) of patients in TRuE-V1 and TRuE-V2, respectively. The most frequently reported adverse events were acne (6.3% [14/221] and 6.6% [15/228]), nasopharyngitis (5.4% [12/221] and 6.1% [14/228]), and pruritus (5.4% [12/221] and 5.3% [12/228]). These findings align with prior subgroup analyses of an earlier phase 2 double- blind RCT of ruxolitinib cream 1.5% that indicated similar improvement in vitiligo among patients with differing skin tones.¹⁷

There are no additional large-scale RCTs examining topical JAK inhibitors with intentional subanalysis of diverse skin tones.^16,17,18 Studies examining topical JAK inhibitors have expanded to be more inclusive, providing hope for the future of topical vitiligo therapeutics for all patients.

Final Thoughts

It is imperative to increase racial/ethnic and skin type diversity in research on JAK inhibitors for vitiligo. While the studies mentioned here are inclusive of an array of races and skin tones, it is crucial that future research continue to expand the number of diverse participants, especially given the increased psychosocial burdens of vitiligo in patients with darker skin types.⁴ Intentional subgroup analyses across skin tones are vital to characterize and unmask potential differences between lighter and darker skin types. This point was exemplified by a 2024 RCT that investigated ritlecitinib efficacy with biomarker analysis across skin types.¹⁹ For patients receiving ritlecitinib 50 mg, IL-9 and IL-22 expression were decreased in darker vs lighter skin tones (P<.05). This intentional and inclusive analysis revealed a potential immunologic mechanism for why darker skin tones respond to JAK inhibitor therapy earlier than lighter skin tones.¹⁹

In the expanding landscape of oral and topical JAK inhibitors for vitiligo, continued efforts to assess these therapies across a range of skin tones and racial/ ethnic groups are critical. The efficacy of JAK inhibitors in other populations, including pediatric patients and patients with refractory segmental disease, have been reported.^20,21 As larger studies are developed based on the success of individual cases, researchers should investigate the efficacy of JAK inhibitors for various vitiligo subtypes (eg, segmental, nonsegmental) and recalcitrant disease and conduct direct comparisons with traditional treatments across diverse skin tones and racial/ethnic subgroup analyses to ensure broad therapeutic applicability.

Vitiligo is a common autoimmune disorder characterized by cutaneous depigmentation that has a substantial impact on patient quality of life.¹ Vitiligo affects approximately 28.5 million individuals globally, with the highest lifetime prevalence occurring in Central Europe and South Asia.² In the United States, Asian American and Hispanic/Latine populations most commonly are affected.³ The accompanying psychosocial burdens of vitiligo are particularly substantial among individuals with darker skin types, as evidenced by higher rates of concomitant anxiety and depression in these patients.⁴ Despite this, patients with skin of color are underrepresented in vitiligo research.²

Treatment algorithms developed based on worldwide expert consensus recommendations provide valuable insights into the management of segmental and nonsegmental vitiligo.⁵ The mainstay therapeutics include topical and oral corticosteroids, topical calcineurin inhibitors, and phototherapy. While vitiligo pathogenesis is not completely understood, recent advances have focused on the role of the Janus kinase (JAK)/signal transducer and activator of transcription pathway. Interferon gamma drives vitiligo pathogenesis through this pathway, upregulating C-X-C motif chemokine ligand 10 and promoting CD8+ T-cell recruitment, resulting in targeted melanocyte destruction.⁶ The emergence of targeted therapeutics may address equity and inclusion gaps. Herein, we highlight innovations in vitiligo treatment with a focus on oral and topical JAK inhibitors.

Oral JAK Inhibitors for Vitiligo

The therapeutic potential of JAK inhibitors for vitiligo was first reported when patients with alopecia areata and comorbid vitiligo experienced repigmentation of the skin following administration of oral ruxolitinib.⁷ Since this discovery, other oral JAK inhibitors have been investigated for vitiligo treatment. A phase 2b randomized clinical trial (RCT) of 364 patients examined oral ritlecitinib, a JAK3 inhibitor, and found it to be effective in treating active nonsegmental vitiligo.⁸ Patients aged 18 to 65 years with active nonsegmental vitiligo that had been present for 3 months or more as well as 4% to 50% body surface area (BSA) affected excluding acral surfaces and at least 0.25% facial involvement were included. Treatment groups received 50 mg (with or without a 100- or 200- mg loading dose), 30 mg, or 10 mg daily for 24 weeks. The primary endpoint measured the percentage change in Facial Vitiligo Area Scoring Index (F-VASI) score. Significant differences in F-VASI percentage change compared with placebo occurred for those in the 50-mg group who received a loading dose (-21.2 vs 2.1 [P<.001]) and those who did not receive a loading dose (–18.5 vs 2.1 [P<.001]) as well as the 30-mg group (-14.6 vs 2.1 [P=.01]). Continued repigmentation of the skin was observed in the 24-week extension period, indicating that longer treatment periods may be necessary for optimal repigmentation results. Ritlecitinib generally was well tolerated, and the most common treatment-emergent adverse events were nasopharyngitis (15.9%), upper respiratory tract infection (11.5%), and headache (8.8%). Most patients identified as White (67.6%), with 23.6% identifying as Asian and 2.7% identifying as Black. The authors stated that continued improvement was observed in the extension period across all skin types; however, the data were not reported.⁸

Upadacitnib, an oral selective JAK1 inhibitor, also has demonstrated efficacy in nonsegmental vitiligo in a phase 2 RCT.⁹ Adult patients (N=185) with nonsegmental vitiligo were randomized to receive upadacitinib 6 mg, 11 mg, or 22 mg or placebo (the placebo group subsequently was switched to upadacitinib 11 mg or 22 mg after 24 weeks). The primary endpoint measured the percentage change in F-VASI score at 24 weeks. The higher doses of upadacitinib resulted in significant changes in F-VASI scored compared with placebo (6 mg: -7.60 [95% CI, -22.18 to 6.97][P=.30]; 11 mg: -21.27 [95% CI, -36.02 to -6.52][P=.01]; 22 mg: -19.60 [95% CI, -35.04 to –4.16][P=.01]). As with ritlecitinib, continued repigmentation was observed beyond the initial 24-week period. Of the 185 participants, 5.9% identified as Black and 13.5% identified as Asian. The investigators reported that the percentage change in F-VASI score was consistent across skin types.⁹ The results of these phase 2 RCTs are encouraging, and we anticipate the findings of 2 phase 3 RCTs for ritlecitinib and upadacitinib that currently are underway (Clinicaltrials.gov identifiers NCT05583526 and NCT06118411).

Topical JAK Inhibitors for Vitiligo

Tofacitinib cream 2%, a selective JAK3 inhibitor, has shown therapeutic potential for treatment of vitiligo. One of the earliest pilot studies on topical tofacitinib examined the efficacy of tofacitinib cream 2% applied twice daily combined with narrowband UVB therapy 3 times weekly for facial vitiligo. The investigators reported repigmentation of the skin in all 11 patients (which included 4 Asian patients and 1 Hispanic patient), with a mean improvement of 70% in F-VASI score (range, 50%-87%).¹⁰ In a nonrandomized cohort study of 16 patients later that year, twice-daily application of tofacitinib cream 2% on facial and nonfacial vitiligo lesions resulted in partial repigmentation in 81.3% of patients: 4 (25%) achieved greater than 90% improvement, 5 (31.3%) achieved improvement of 25% to 75%, and 4 (25%) achieved 5% to 15% improvement.¹¹ The researchers also found that tofacitinib cream 2% was significantly more effective in facial than nonfacial lesions (P=.02).

While tofacitinib has shown promise in early studies, recent advancements have led to US Food and Drug Administration approval of ruxolitinib cream 1.5%, another topical JAK inhibitor that has undergone robust clinical testing for vitiligo.^12-14 Ruxolitinib, a JAK1, JAK2, and JAK3 inhibitor, is the first and only US Food and Drug Administration–approved topical JAK inhibitor for vitiligo.^14,15 Two phase 3, double-blind, vehicle-controlled trials of identical design conducted across 101 centers in North America and Europe (TRuE-V1 and TRuE-V2) assessed the efficacy of ruxolitinib cream 1.5% in 674 patients aged 12 years and older with nonsegmental vitiligo covering 10% or lower total BSA.¹³ In both trials, twice-daily application of topical ruxolitinib resulted in greater facial repigmentation and improvement in F-VASI75 score (ie, a reduction of at least 75% from baseline) at 24 weeks in 29.9% (66/221) and 30.1% (69/222) of patients in TRuE-V1 and TRuE-V2, respectively. Continued application through 52 weeks resulted in F-VASI75 response in 52.6% (91/173) and 48.0% (85/177) of patients in TRuE-V1 and TRuE-V2, respectively. The most frequently reported adverse events were acne (6.3% [14/221] and 6.6% [15/228]), nasopharyngitis (5.4% [12/221] and 6.1% [14/228]), and pruritus (5.4% [12/221] and 5.3% [12/228]). These findings align with prior subgroup analyses of an earlier phase 2 double- blind RCT of ruxolitinib cream 1.5% that indicated similar improvement in vitiligo among patients with differing skin tones.¹⁷

There are no additional large-scale RCTs examining topical JAK inhibitors with intentional subanalysis of diverse skin tones.^16,17,18 Studies examining topical JAK inhibitors have expanded to be more inclusive, providing hope for the future of topical vitiligo therapeutics for all patients.

Final Thoughts

It is imperative to increase racial/ethnic and skin type diversity in research on JAK inhibitors for vitiligo. While the studies mentioned here are inclusive of an array of races and skin tones, it is crucial that future research continue to expand the number of diverse participants, especially given the increased psychosocial burdens of vitiligo in patients with darker skin types.⁴ Intentional subgroup analyses across skin tones are vital to characterize and unmask potential differences between lighter and darker skin types. This point was exemplified by a 2024 RCT that investigated ritlecitinib efficacy with biomarker analysis across skin types.¹⁹ For patients receiving ritlecitinib 50 mg, IL-9 and IL-22 expression were decreased in darker vs lighter skin tones (P<.05). This intentional and inclusive analysis revealed a potential immunologic mechanism for why darker skin tones respond to JAK inhibitor therapy earlier than lighter skin tones.¹⁹

In the expanding landscape of oral and topical JAK inhibitors for vitiligo, continued efforts to assess these therapies across a range of skin tones and racial/ ethnic groups are critical. The efficacy of JAK inhibitors in other populations, including pediatric patients and patients with refractory segmental disease, have been reported.^20,21 As larger studies are developed based on the success of individual cases, researchers should investigate the efficacy of JAK inhibitors for various vitiligo subtypes (eg, segmental, nonsegmental) and recalcitrant disease and conduct direct comparisons with traditional treatments across diverse skin tones and racial/ethnic subgroup analyses to ensure broad therapeutic applicability.

Advances in understanding the pathophysiology of vitiligo are transforming patient management, offering new hope for individuals with mild, moderate, and even severe forms of the disease, delegates heard at a recent conference, the Dermatology Days of Paris 2024, organized by the French Society of Dermatology.

A Distinct Disease

An estimated 65% of patients with vitiligo in Europe have been told that their disease is untreatable, according to a recent international study, and this figure rises to 75% in France, Julien Seneschal, MD, PhD, professor of dermatology at Bordeaux University Hospital in Bordeaux, France, told the audience during his presentation. 

“This is a message we must change,” he said.

The survey also revealed that in France, even when treatment is offered, 80% of patients do not receive appropriate care. However, treatments do exist, and novel approaches are revolutionizing the management of patients, whatever the degree of severity, he explained.

As a specialist in inflammatory and autoimmune skin diseases, he stressed that these advances are important because vitiligo is a distinct disease and not merely a cosmetic issue. When widespread, it has a significant impact on quality of life and can lead to depression, anxiety, and even suicidal thoughts, even though it does not affect life expectancy.

 

Updated Guidelines

Since October 2023, new international guidelines for vitiligo management have defined a therapeutic algorithm.

“Nowadays, we place the patient at the center of therapeutic decision-making,” Seneschal said. It is essential to educate patients about the disease and take the time to understand their treatment goals.

For patients with mild vitiligo that does not affect quality of life, simple monitoring may suffice.

However, when a decision is made to pursue treatment, its goals should be:

• Halting disease progression and melanocyte loss 
• Achieving repigmentation (a process that can take 6-24 months) 
• Preventing relapse after treatment discontinuation 

For moderate cases affecting less than 10% of the skin surface, localized treatment is recommended. Previously, topical corticosteroids were used for body lesions, while tacrolimus 0.1% (off-label) was often prescribed for the face and neck. However, as of March 2024, tacrolimus has been officially approved for use in patients aged ≥ 2 years.

In more severe, generalized, and/or active cases, oral treatments such as corticosteroids taken twice weekly for 12-24 weeks can stabilize the disease in 80% of cases (off-label use). Other off-label options include methotrexate, cyclosporine, and tetracyclines.

 

Targeted Therapies

Recent targeted therapies have significantly advanced the treatment of moderate to severe vitiligo. Since January 2024, the Janus kinase 1 (JAK1)/JAK2 inhibitor ruxolitinib cream has been available in community pharmacies after previously being restricted to hospital use, Seneschal said, and can have spectacular results if previous treatments have failed.

Ruxolitinib is approved for patients aged > 12 years with nonsegmental vitiligo and facial involvement, covering up to 10% of the body surface area. Treatment typically lasts 6 months to 1 year.

 

Key Findings

The cream-formulated drug has been demonstrated effective in reducing inflammation in two phase 3 clinical trials published in the New England Journal of Medicine that demonstrated its efficacy and safety in patients aged ≥ 12 years. The treatment was well tolerated despite some mild acne-like reactions in 8% of patients. It was shown to be very effective on the face, with a reduction of over 75% in facial lesions in more than 50% of patients, and had good effectiveness on the body, with a 50% decrease in lesions in more than 50% of patients on the body, trunk, arms, and legs, excluding hands and feet.

“Areas like the underarms, hands, and feet are more resistant to treatment,” Seneschal noted.

Although some improvement continues after 1 year, disease recurrence is common if treatment is stopped: Only 40% of patients maintain therapeutic benefits in the year following discontinuation.

“It is therefore important to consider the value of continuing treatment in order to achieve better efficacy or to maintain the repigmentation obtained,” Seneschal said.

He stressed that all treatments should be paired with phototherapy, typically narrowband UVB, to accelerate repigmentation. “There is no increased skin cancer risk in vitiligo patients treated with narrowband UVB,” Seneschal said.

 

New Therapies

Emerging treatments under development, including injectable biologics alone or in combination with phototherapy, show great promise, he said. Oral JAK inhibitors such as ritlecitinib, upadacitinib, and povorcitinib are also under investigation.

In particular, ritlecitinib, a JAK3/TEC pathway inhibitor, has shown significant reductions in affected skin area in severely affected patients in a phase 2b trial. Phase 3 trials are now underway.

On the safety profile of JAK inhibitors, Seneschal said that studies are reassuring but highlighted the need to monitor cardiovascular, thromboembolic, and infectious risks.

“The question of safety is important because vitiligo is a visible but nonsevere condition, and we do not want to expose patients to unnecessary risks,” added Gaëlle Quéreux, MD, PhD, president of the French Society of Dermatology.

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

Advances in understanding the pathophysiology of vitiligo are transforming patient management, offering new hope for individuals with mild, moderate, and even severe forms of the disease, delegates heard at a recent conference, the Dermatology Days of Paris 2024, organized by the French Society of Dermatology.

A Distinct Disease

An estimated 65% of patients with vitiligo in Europe have been told that their disease is untreatable, according to a recent international study, and this figure rises to 75% in France, Julien Seneschal, MD, PhD, professor of dermatology at Bordeaux University Hospital in Bordeaux, France, told the audience during his presentation. 

“This is a message we must change,” he said.

The survey also revealed that in France, even when treatment is offered, 80% of patients do not receive appropriate care. However, treatments do exist, and novel approaches are revolutionizing the management of patients, whatever the degree of severity, he explained.

As a specialist in inflammatory and autoimmune skin diseases, he stressed that these advances are important because vitiligo is a distinct disease and not merely a cosmetic issue. When widespread, it has a significant impact on quality of life and can lead to depression, anxiety, and even suicidal thoughts, even though it does not affect life expectancy.

 

Updated Guidelines

Since October 2023, new international guidelines for vitiligo management have defined a therapeutic algorithm.

“Nowadays, we place the patient at the center of therapeutic decision-making,” Seneschal said. It is essential to educate patients about the disease and take the time to understand their treatment goals.

For patients with mild vitiligo that does not affect quality of life, simple monitoring may suffice.

However, when a decision is made to pursue treatment, its goals should be:

• Halting disease progression and melanocyte loss 
• Achieving repigmentation (a process that can take 6-24 months) 
• Preventing relapse after treatment discontinuation 

For moderate cases affecting less than 10% of the skin surface, localized treatment is recommended. Previously, topical corticosteroids were used for body lesions, while tacrolimus 0.1% (off-label) was often prescribed for the face and neck. However, as of March 2024, tacrolimus has been officially approved for use in patients aged ≥ 2 years.

In more severe, generalized, and/or active cases, oral treatments such as corticosteroids taken twice weekly for 12-24 weeks can stabilize the disease in 80% of cases (off-label use). Other off-label options include methotrexate, cyclosporine, and tetracyclines.

 

Targeted Therapies

Recent targeted therapies have significantly advanced the treatment of moderate to severe vitiligo. Since January 2024, the Janus kinase 1 (JAK1)/JAK2 inhibitor ruxolitinib cream has been available in community pharmacies after previously being restricted to hospital use, Seneschal said, and can have spectacular results if previous treatments have failed.

Ruxolitinib is approved for patients aged > 12 years with nonsegmental vitiligo and facial involvement, covering up to 10% of the body surface area. Treatment typically lasts 6 months to 1 year.

 

Key Findings

The cream-formulated drug has been demonstrated effective in reducing inflammation in two phase 3 clinical trials published in the New England Journal of Medicine that demonstrated its efficacy and safety in patients aged ≥ 12 years. The treatment was well tolerated despite some mild acne-like reactions in 8% of patients. It was shown to be very effective on the face, with a reduction of over 75% in facial lesions in more than 50% of patients, and had good effectiveness on the body, with a 50% decrease in lesions in more than 50% of patients on the body, trunk, arms, and legs, excluding hands and feet.

“Areas like the underarms, hands, and feet are more resistant to treatment,” Seneschal noted.

Although some improvement continues after 1 year, disease recurrence is common if treatment is stopped: Only 40% of patients maintain therapeutic benefits in the year following discontinuation.

“It is therefore important to consider the value of continuing treatment in order to achieve better efficacy or to maintain the repigmentation obtained,” Seneschal said.

He stressed that all treatments should be paired with phototherapy, typically narrowband UVB, to accelerate repigmentation. “There is no increased skin cancer risk in vitiligo patients treated with narrowband UVB,” Seneschal said.

 

New Therapies

Emerging treatments under development, including injectable biologics alone or in combination with phototherapy, show great promise, he said. Oral JAK inhibitors such as ritlecitinib, upadacitinib, and povorcitinib are also under investigation.

In particular, ritlecitinib, a JAK3/TEC pathway inhibitor, has shown significant reductions in affected skin area in severely affected patients in a phase 2b trial. Phase 3 trials are now underway.

On the safety profile of JAK inhibitors, Seneschal said that studies are reassuring but highlighted the need to monitor cardiovascular, thromboembolic, and infectious risks.

“The question of safety is important because vitiligo is a visible but nonsevere condition, and we do not want to expose patients to unnecessary risks,” added Gaëlle Quéreux, MD, PhD, president of the French Society of Dermatology.

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

Advances in understanding the pathophysiology of vitiligo are transforming patient management, offering new hope for individuals with mild, moderate, and even severe forms of the disease, delegates heard at a recent conference, the Dermatology Days of Paris 2024, organized by the French Society of Dermatology.

A Distinct Disease

An estimated 65% of patients with vitiligo in Europe have been told that their disease is untreatable, according to a recent international study, and this figure rises to 75% in France, Julien Seneschal, MD, PhD, professor of dermatology at Bordeaux University Hospital in Bordeaux, France, told the audience during his presentation. 

“This is a message we must change,” he said.

The survey also revealed that in France, even when treatment is offered, 80% of patients do not receive appropriate care. However, treatments do exist, and novel approaches are revolutionizing the management of patients, whatever the degree of severity, he explained.

As a specialist in inflammatory and autoimmune skin diseases, he stressed that these advances are important because vitiligo is a distinct disease and not merely a cosmetic issue. When widespread, it has a significant impact on quality of life and can lead to depression, anxiety, and even suicidal thoughts, even though it does not affect life expectancy.

 

Updated Guidelines

Since October 2023, new international guidelines for vitiligo management have defined a therapeutic algorithm.

“Nowadays, we place the patient at the center of therapeutic decision-making,” Seneschal said. It is essential to educate patients about the disease and take the time to understand their treatment goals.

For patients with mild vitiligo that does not affect quality of life, simple monitoring may suffice.

However, when a decision is made to pursue treatment, its goals should be:

• Halting disease progression and melanocyte loss 
• Achieving repigmentation (a process that can take 6-24 months) 
• Preventing relapse after treatment discontinuation 

For moderate cases affecting less than 10% of the skin surface, localized treatment is recommended. Previously, topical corticosteroids were used for body lesions, while tacrolimus 0.1% (off-label) was often prescribed for the face and neck. However, as of March 2024, tacrolimus has been officially approved for use in patients aged ≥ 2 years.

In more severe, generalized, and/or active cases, oral treatments such as corticosteroids taken twice weekly for 12-24 weeks can stabilize the disease in 80% of cases (off-label use). Other off-label options include methotrexate, cyclosporine, and tetracyclines.

 

Targeted Therapies

Recent targeted therapies have significantly advanced the treatment of moderate to severe vitiligo. Since January 2024, the Janus kinase 1 (JAK1)/JAK2 inhibitor ruxolitinib cream has been available in community pharmacies after previously being restricted to hospital use, Seneschal said, and can have spectacular results if previous treatments have failed.

Ruxolitinib is approved for patients aged > 12 years with nonsegmental vitiligo and facial involvement, covering up to 10% of the body surface area. Treatment typically lasts 6 months to 1 year.

 

Key Findings

The cream-formulated drug has been demonstrated effective in reducing inflammation in two phase 3 clinical trials published in the New England Journal of Medicine that demonstrated its efficacy and safety in patients aged ≥ 12 years. The treatment was well tolerated despite some mild acne-like reactions in 8% of patients. It was shown to be very effective on the face, with a reduction of over 75% in facial lesions in more than 50% of patients, and had good effectiveness on the body, with a 50% decrease in lesions in more than 50% of patients on the body, trunk, arms, and legs, excluding hands and feet.

“Areas like the underarms, hands, and feet are more resistant to treatment,” Seneschal noted.

Although some improvement continues after 1 year, disease recurrence is common if treatment is stopped: Only 40% of patients maintain therapeutic benefits in the year following discontinuation.

“It is therefore important to consider the value of continuing treatment in order to achieve better efficacy or to maintain the repigmentation obtained,” Seneschal said.

He stressed that all treatments should be paired with phototherapy, typically narrowband UVB, to accelerate repigmentation. “There is no increased skin cancer risk in vitiligo patients treated with narrowband UVB,” Seneschal said.

 

New Therapies

Emerging treatments under development, including injectable biologics alone or in combination with phototherapy, show great promise, he said. Oral JAK inhibitors such as ritlecitinib, upadacitinib, and povorcitinib are also under investigation.

In particular, ritlecitinib, a JAK3/TEC pathway inhibitor, has shown significant reductions in affected skin area in severely affected patients in a phase 2b trial. Phase 3 trials are now underway.

On the safety profile of JAK inhibitors, Seneschal said that studies are reassuring but highlighted the need to monitor cardiovascular, thromboembolic, and infectious risks.

“The question of safety is important because vitiligo is a visible but nonsevere condition, and we do not want to expose patients to unnecessary risks,” added Gaëlle Quéreux, MD, PhD, president of the French Society of Dermatology.

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

Prurigo nodularis (PN) is a chronic inflammatory skin condition characterized by firm hyperkeratotic nodules that develop when patients persistently scratch or rub intensely itchy areas of the skin. This potent itch-scratch cycle can be traced back to a dysfunctional interplay between cutaneous nerve fibers and the local immune environment.^1-3 Pruritis lasting at least 6 weeks is a hallmark symptom of PN and can be accompanied by pain and/or a burning sensation.⁴ The lesions are symmetrically distributed in areas that are easy to scratch (eg, arms, legs, trunk), typically sparing the face, palms, and soles; however, facial lesions have been reported in pediatric patients with PN, who also are more likely to have back, hand, and foot involvement.^5,6

Prurigo nodularis can greatly affect patients’ quality of life, leading to increased rates of depression and anxiety.^7-9 Patients with severe symptoms also report increased sleep disturbance, distraction from work, self-consciousness leading to social isolation, and missed days of work/school.⁹ In one study, patients with PN reported missing at least 1 day of work, school, training, or learning; giving up a leisure activity or sport; or refusing an invitation to dinner or a party in the past 3 months due to the disease.¹⁰

Epidemiology

Prurigo nodularis has a prevalence of 72 per 100,000 individuals in the United States,¹¹ most commonly affecting adults aged 51 to 65 years and disproportionately affecting African American and female patients.^12,13 Most patients with PN experience a 2-year delay in diagnosis after initial onset of symptoms.¹⁰ Adults with PN have an increased likelihood of having other dermatologic conditions, including atopic dermatitis (AD) and psoriasis.¹¹ Nearly two-thirds of pediatric patients with PN present with AD, and those with AD showed more resistance to first-line treatment options.⁵

Key Clinical Features

Compared to White patients, who typically present with lesions that appear erythematous or pink, patients with darker skin tones may present with hyperpigmented nodules that are larger and darker.¹² The pruritic nodules often show signs of scratching or picking (eg, excoriations, lichenification, and angulated erosions).⁴

Worth Noting

Diagnosis of PN is made clinically, but skin biopsy may be helpful to rule out alternative diseases. Histologically, the hairy palm sign may be present in addition to other histologic features commonly associated with excessive scratching or rubbing of the skin.

Patients with PN have a high risk for HIV, which is not suprising considering HIV is a known systemic cause of generalized chronic pruritus. Other associations include type 2 diabetes mellitus and thyroid, kidney, and liver disease.^11,13 Work-up for patients with PN should include a complete blood count with differential; liver and renal function testing; and testing for C-reactive protein, thyroid-stimulating hormone, and lactate dehydrogenase.^4,14 Hemoglobin A1c and HIV testing as well as a hepatitis panel also should be considered when appropriate. Because generalized pruritus may be a sign of malignancy, chest radiography and lymph node and abdominal ultrasonography should be performed in patients who have experienced itch for less than 1 year along with B symptoms (fever, night sweats, ≥10% weight loss over 6 months, fatigue).¹⁴ Frequent scratching can disrupt the skin barrier, contributing to the increased risk for skin infections.¹³ All patients with a suspected PN diagnosis also should undergo screening for depression and anxiety, as patients with PN are at an increased risk for these conditions.⁴

Treatment of PN starts with breaking the itch-scratch cycle by addressing the underlying cause of the pruritus. Therapies are focused on addressing the immunologic and neural components of the disease. Topical treatments include moderate to strong corticosteroids, calcineurin inhibitors (tacrolimus or pimecrolimus), capsaicin, and antipruritic emollients. Systemic agents include phototherapy (narrowband UVB or excimer laser), gabapentin, pregabalin, paroxetine, and amitriptyline to address the neural component of itch. Methotrexate or cyclosporine can be used to address the immunologic component of PN and diminish the itch. That said, methotrexate and cyclosporine often are inadequate to control pruritus.¹⁰ Of note, sedating antihistamines are not effective in treating itch in PN but can be used as an adjuvant therapy for sleep disturbances in these patients.¹⁵

The only drugs currently approved by the US Food and Drug Administration to treat PN are the biologics dupilumab (targeting the IL-4 receptor) approved in 2022 and nemolizumab (targeting the IL-31 receptor) approved in 2024.^16-18 The evidence that these injectable biologics work is heartening in a condition that has historically been very challenging to treat.^16,18 It should be noted that the high cost of these 2 medications can restrict access to care for patients who are uninsured or underinsured.

Resolution of a prurigo nodule may result in a hyperpigmented macule taking months to years to fade.

Health Disparity Highlight

Patients with PN have a considerable comorbidity burden, negative impact on quality of life, and increased health care utilization rates.¹² Prurigo nodularis is 3.4 times more common in Black patients than White patients.¹³ Black patients with PN have increased mortality, higher health care utilization rates, and increased systemic inflammation compared to White patients.^12,19,20

Social drivers of health (eg, socioeconomic challenges, education, access to high-quality health care) likely contribute to PN. Historically, there has been a paucity of research on PN, as with most conditions that disproportionately affect patients with skin of color. Several PN clinical trials currently are underway to explore additional therapeutic options.¹¹

Prurigo nodularis (PN) is a chronic inflammatory skin condition characterized by firm hyperkeratotic nodules that develop when patients persistently scratch or rub intensely itchy areas of the skin. This potent itch-scratch cycle can be traced back to a dysfunctional interplay between cutaneous nerve fibers and the local immune environment.^1-3 Pruritis lasting at least 6 weeks is a hallmark symptom of PN and can be accompanied by pain and/or a burning sensation.⁴ The lesions are symmetrically distributed in areas that are easy to scratch (eg, arms, legs, trunk), typically sparing the face, palms, and soles; however, facial lesions have been reported in pediatric patients with PN, who also are more likely to have back, hand, and foot involvement.^5,6

Prurigo nodularis can greatly affect patients’ quality of life, leading to increased rates of depression and anxiety.^7-9 Patients with severe symptoms also report increased sleep disturbance, distraction from work, self-consciousness leading to social isolation, and missed days of work/school.⁹ In one study, patients with PN reported missing at least 1 day of work, school, training, or learning; giving up a leisure activity or sport; or refusing an invitation to dinner or a party in the past 3 months due to the disease.¹⁰

Epidemiology

Prurigo nodularis has a prevalence of 72 per 100,000 individuals in the United States,¹¹ most commonly affecting adults aged 51 to 65 years and disproportionately affecting African American and female patients.^12,13 Most patients with PN experience a 2-year delay in diagnosis after initial onset of symptoms.¹⁰ Adults with PN have an increased likelihood of having other dermatologic conditions, including atopic dermatitis (AD) and psoriasis.¹¹ Nearly two-thirds of pediatric patients with PN present with AD, and those with AD showed more resistance to first-line treatment options.⁵

Key Clinical Features

Compared to White patients, who typically present with lesions that appear erythematous or pink, patients with darker skin tones may present with hyperpigmented nodules that are larger and darker.¹² The pruritic nodules often show signs of scratching or picking (eg, excoriations, lichenification, and angulated erosions).⁴

Worth Noting

Diagnosis of PN is made clinically, but skin biopsy may be helpful to rule out alternative diseases. Histologically, the hairy palm sign may be present in addition to other histologic features commonly associated with excessive scratching or rubbing of the skin.

Patients with PN have a high risk for HIV, which is not suprising considering HIV is a known systemic cause of generalized chronic pruritus. Other associations include type 2 diabetes mellitus and thyroid, kidney, and liver disease.^11,13 Work-up for patients with PN should include a complete blood count with differential; liver and renal function testing; and testing for C-reactive protein, thyroid-stimulating hormone, and lactate dehydrogenase.^4,14 Hemoglobin A1c and HIV testing as well as a hepatitis panel also should be considered when appropriate. Because generalized pruritus may be a sign of malignancy, chest radiography and lymph node and abdominal ultrasonography should be performed in patients who have experienced itch for less than 1 year along with B symptoms (fever, night sweats, ≥10% weight loss over 6 months, fatigue).¹⁴ Frequent scratching can disrupt the skin barrier, contributing to the increased risk for skin infections.¹³ All patients with a suspected PN diagnosis also should undergo screening for depression and anxiety, as patients with PN are at an increased risk for these conditions.⁴

Treatment of PN starts with breaking the itch-scratch cycle by addressing the underlying cause of the pruritus. Therapies are focused on addressing the immunologic and neural components of the disease. Topical treatments include moderate to strong corticosteroids, calcineurin inhibitors (tacrolimus or pimecrolimus), capsaicin, and antipruritic emollients. Systemic agents include phototherapy (narrowband UVB or excimer laser), gabapentin, pregabalin, paroxetine, and amitriptyline to address the neural component of itch. Methotrexate or cyclosporine can be used to address the immunologic component of PN and diminish the itch. That said, methotrexate and cyclosporine often are inadequate to control pruritus.¹⁰ Of note, sedating antihistamines are not effective in treating itch in PN but can be used as an adjuvant therapy for sleep disturbances in these patients.¹⁵

The only drugs currently approved by the US Food and Drug Administration to treat PN are the biologics dupilumab (targeting the IL-4 receptor) approved in 2022 and nemolizumab (targeting the IL-31 receptor) approved in 2024.^16-18 The evidence that these injectable biologics work is heartening in a condition that has historically been very challenging to treat.^16,18 It should be noted that the high cost of these 2 medications can restrict access to care for patients who are uninsured or underinsured.

Resolution of a prurigo nodule may result in a hyperpigmented macule taking months to years to fade.

Health Disparity Highlight

Patients with PN have a considerable comorbidity burden, negative impact on quality of life, and increased health care utilization rates.¹² Prurigo nodularis is 3.4 times more common in Black patients than White patients.¹³ Black patients with PN have increased mortality, higher health care utilization rates, and increased systemic inflammation compared to White patients.^12,19,20

Social drivers of health (eg, socioeconomic challenges, education, access to high-quality health care) likely contribute to PN. Historically, there has been a paucity of research on PN, as with most conditions that disproportionately affect patients with skin of color. Several PN clinical trials currently are underway to explore additional therapeutic options.¹¹

Prurigo nodularis (PN) is a chronic inflammatory skin condition characterized by firm hyperkeratotic nodules that develop when patients persistently scratch or rub intensely itchy areas of the skin. This potent itch-scratch cycle can be traced back to a dysfunctional interplay between cutaneous nerve fibers and the local immune environment.^1-3 Pruritis lasting at least 6 weeks is a hallmark symptom of PN and can be accompanied by pain and/or a burning sensation.⁴ The lesions are symmetrically distributed in areas that are easy to scratch (eg, arms, legs, trunk), typically sparing the face, palms, and soles; however, facial lesions have been reported in pediatric patients with PN, who also are more likely to have back, hand, and foot involvement.^5,6

Prurigo nodularis can greatly affect patients’ quality of life, leading to increased rates of depression and anxiety.^7-9 Patients with severe symptoms also report increased sleep disturbance, distraction from work, self-consciousness leading to social isolation, and missed days of work/school.⁹ In one study, patients with PN reported missing at least 1 day of work, school, training, or learning; giving up a leisure activity or sport; or refusing an invitation to dinner or a party in the past 3 months due to the disease.¹⁰

Epidemiology

Prurigo nodularis has a prevalence of 72 per 100,000 individuals in the United States,¹¹ most commonly affecting adults aged 51 to 65 years and disproportionately affecting African American and female patients.^12,13 Most patients with PN experience a 2-year delay in diagnosis after initial onset of symptoms.¹⁰ Adults with PN have an increased likelihood of having other dermatologic conditions, including atopic dermatitis (AD) and psoriasis.¹¹ Nearly two-thirds of pediatric patients with PN present with AD, and those with AD showed more resistance to first-line treatment options.⁵

Key Clinical Features

Compared to White patients, who typically present with lesions that appear erythematous or pink, patients with darker skin tones may present with hyperpigmented nodules that are larger and darker.¹² The pruritic nodules often show signs of scratching or picking (eg, excoriations, lichenification, and angulated erosions).⁴

Worth Noting

Diagnosis of PN is made clinically, but skin biopsy may be helpful to rule out alternative diseases. Histologically, the hairy palm sign may be present in addition to other histologic features commonly associated with excessive scratching or rubbing of the skin.

Patients with PN have a high risk for HIV, which is not suprising considering HIV is a known systemic cause of generalized chronic pruritus. Other associations include type 2 diabetes mellitus and thyroid, kidney, and liver disease.^11,13 Work-up for patients with PN should include a complete blood count with differential; liver and renal function testing; and testing for C-reactive protein, thyroid-stimulating hormone, and lactate dehydrogenase.^4,14 Hemoglobin A1c and HIV testing as well as a hepatitis panel also should be considered when appropriate. Because generalized pruritus may be a sign of malignancy, chest radiography and lymph node and abdominal ultrasonography should be performed in patients who have experienced itch for less than 1 year along with B symptoms (fever, night sweats, ≥10% weight loss over 6 months, fatigue).¹⁴ Frequent scratching can disrupt the skin barrier, contributing to the increased risk for skin infections.¹³ All patients with a suspected PN diagnosis also should undergo screening for depression and anxiety, as patients with PN are at an increased risk for these conditions.⁴

Treatment of PN starts with breaking the itch-scratch cycle by addressing the underlying cause of the pruritus. Therapies are focused on addressing the immunologic and neural components of the disease. Topical treatments include moderate to strong corticosteroids, calcineurin inhibitors (tacrolimus or pimecrolimus), capsaicin, and antipruritic emollients. Systemic agents include phototherapy (narrowband UVB or excimer laser), gabapentin, pregabalin, paroxetine, and amitriptyline to address the neural component of itch. Methotrexate or cyclosporine can be used to address the immunologic component of PN and diminish the itch. That said, methotrexate and cyclosporine often are inadequate to control pruritus.¹⁰ Of note, sedating antihistamines are not effective in treating itch in PN but can be used as an adjuvant therapy for sleep disturbances in these patients.¹⁵

The only drugs currently approved by the US Food and Drug Administration to treat PN are the biologics dupilumab (targeting the IL-4 receptor) approved in 2022 and nemolizumab (targeting the IL-31 receptor) approved in 2024.^16-18 The evidence that these injectable biologics work is heartening in a condition that has historically been very challenging to treat.^16,18 It should be noted that the high cost of these 2 medications can restrict access to care for patients who are uninsured or underinsured.

Resolution of a prurigo nodule may result in a hyperpigmented macule taking months to years to fade.

Health Disparity Highlight

Patients with PN have a considerable comorbidity burden, negative impact on quality of life, and increased health care utilization rates.¹² Prurigo nodularis is 3.4 times more common in Black patients than White patients.¹³ Black patients with PN have increased mortality, higher health care utilization rates, and increased systemic inflammation compared to White patients.^12,19,20

Social drivers of health (eg, socioeconomic challenges, education, access to high-quality health care) likely contribute to PN. Historically, there has been a paucity of research on PN, as with most conditions that disproportionately affect patients with skin of color. Several PN clinical trials currently are underway to explore additional therapeutic options.¹¹