Pigmentation Disorders

A topical cream formulation of the Janus kinase inhibitor ruxolitinib was superior to its vehicle for treating vitiligo across all primary and secondary endpoints in two multicenter phase 3 trials presented together at the annual meeting of the European Academy of Dermatology and Venereology.

On the primary endpoint of F-VASI 75 (75% improvement in the Facial and Vitiligo Scoring Index), rates were nearly four times higher at 24 weeks in one trial (29.9% vs. 7.5%; P < .0001) and more than twice as great in the other (29.9% vs. 12.9%; P < .01).

“The larger phase 3 trials confirm the previous phase 2 findings,” reported David Rosmarin, MD, vice chairman for research and education, department of dermatology, Tufts Medical Center, Boston. These findings not only include substantial clinical efficacy but good tolerability with “no serious treatment-related adverse events,” he noted.
 

600 patients randomized

In one of the trials, called TRuE-V1, 330 patients with vitiligo were randomly assigned in a 2:1 ratio to 1.5% ruxolitinib or vehicle applied twice daily. In the other trial, called TRuE-V2, 344 patients were randomly assigned. The participating centers were in Europe and North America.

Patients aged 12 years or older with nonsegmental vitiligo and depigmentation covering no more than 10% of the total body surface area were eligible. The mean baseline F-VASI values were 1.0. The mean total VASI (T-FASI) values were 6.5. On those enrolled, half were female, 11% were adolescents, and 73% had Fitzpatrick skin phototypes III-VI.

Ruxolitinib cream provided near-complete vitiligo clearance (F-VASI 90) on the face at 24 weeks in only about 15% of patients, but this was several times higher than the 2% achieved on vehicle in the TRuE-V1 (P < .01) and the TRuE-V2 trials (P < .05), respectively.

F-VASI 50 response rates greater than 50%

For F-VASI 50, the response rate with ruxolitinib in both studies was approximately 51%. Relative to the 17.2% response on vehicle in TRuE-v1 and 23.4% in TRuE-V2 (both P < .0001 vs. active therapy), the advantage of the topical JAK inhibitor was considered to be a clinically meaningful, not just significant from a statistical standpoint.

In fact, improvement on the 5-point Vitiligo Noticeability Scale “also supported a clinically meaningful benefit,” Dr. Rosmarin reported. When those achieving a score of 4 (much less noticeable) or 5 (no longer noticeable), the response rates at 24 weeks were 24.5% and 21.6% in the TRuE-V1 and TRuE-V2 trials, respectively. Again, these response rates were several times greater than the 3.3% (P < .001) and 6.6% (P < .01) observed in the vehicle arms of TRuE-V1 and TRuE-V2 (P < .01), respectively.

Treatment-related adverse events were infrequent. The most common were acne at the application site, which occurred in about 5% of patients receiving ruxolitinib (vs. 2% or fewer of those receiving vehicle) and pruritus, which also occurred in about 5% of patients. However, the rates of pruritus among those on placebo reached 4% in TRuE-V1 and 2% in TRuE-V2 trials.

In vitiligo, where there has been recent progress in understanding the pathophysiology, loss of melanocytes in immune dysregulation has been linked to activation of the JAK signaling pathway, according to Dr. Rosmarin. In the 52-week phase 2 trial with 205 patients, ruxolitinib was associated with a sustained response and no serious treatment-related adverse events.
 

52-week data might show more benefit

Patients are continuing to be followed in the TRuE-V1 and TRuE-V-2 trials. Based on the phase 2 data and on the progressive improvement still being observed at the end of 24 weeks in the phase 3 trials, Dr. Rosmarin expects 52-week results be valuable in understanding the clinical role of ruxolitinib.

“We will be looking for further improvement in response as we follow these patients out to 1 year,” he said.

This further follow-up is important, agreed Iltefat Hamzavi, MD, senior staff physician, department of dermatology, Henry Ford Hospital, Detroit.

Despite the promise of perhaps other JAK inhibitors, “we still need to understand how long it will take for the drug to offer optimal results. We already know that is more than 24 weeks,” said Dr. Hamzavi, who has been involved in the clinical trials with this drug but was not involved with the TRuE-V1 or -V2 trials.

He also said more follow-up is needed to understand the duration of effect. He is, however, optimistic about the clinical role of this mechanism for treatment of vitiligo.

“I do think that JAK inhibitors show a lot of promise [in vitiligo] for certain locations of the body,” he said.

Given the limited treatment options for effective and prolonged improvement in vitiligo, both Dr. Hamzavi and Dr. Rosmarin indicated an effective topical cream is likely to be considered by physicians and patients to be a substantial advance.

On Sept. 21, ruxolitinib (Opzelura) 1.5% cream was approved by the Food and Drug Administration for the short-term treatment of mild to moderate atopic dermatitis in children and adults ages 12 years and older – the first FDA approval of this product.

Dr. Rosmarin reported financial relationships with more than 20 pharmaceutical companies, including Incyte, which provided funding for the TRuE-V1 and -V2 trials. Dr. Hamzavi reported financial relationships with more than 15 companies with pharmaceutical or cosmetic products, including Incyte.

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

A topical cream formulation of the Janus kinase inhibitor ruxolitinib was superior to its vehicle for treating vitiligo across all primary and secondary endpoints in two multicenter phase 3 trials presented together at the annual meeting of the European Academy of Dermatology and Venereology.

On the primary endpoint of F-VASI 75 (75% improvement in the Facial and Vitiligo Scoring Index), rates were nearly four times higher at 24 weeks in one trial (29.9% vs. 7.5%; P < .0001) and more than twice as great in the other (29.9% vs. 12.9%; P < .01).

“The larger phase 3 trials confirm the previous phase 2 findings,” reported David Rosmarin, MD, vice chairman for research and education, department of dermatology, Tufts Medical Center, Boston. These findings not only include substantial clinical efficacy but good tolerability with “no serious treatment-related adverse events,” he noted.
 

600 patients randomized

In one of the trials, called TRuE-V1, 330 patients with vitiligo were randomly assigned in a 2:1 ratio to 1.5% ruxolitinib or vehicle applied twice daily. In the other trial, called TRuE-V2, 344 patients were randomly assigned. The participating centers were in Europe and North America.

Patients aged 12 years or older with nonsegmental vitiligo and depigmentation covering no more than 10% of the total body surface area were eligible. The mean baseline F-VASI values were 1.0. The mean total VASI (T-FASI) values were 6.5. On those enrolled, half were female, 11% were adolescents, and 73% had Fitzpatrick skin phototypes III-VI.

Ruxolitinib cream provided near-complete vitiligo clearance (F-VASI 90) on the face at 24 weeks in only about 15% of patients, but this was several times higher than the 2% achieved on vehicle in the TRuE-V1 (P < .01) and the TRuE-V2 trials (P < .05), respectively.

F-VASI 50 response rates greater than 50%

For F-VASI 50, the response rate with ruxolitinib in both studies was approximately 51%. Relative to the 17.2% response on vehicle in TRuE-v1 and 23.4% in TRuE-V2 (both P < .0001 vs. active therapy), the advantage of the topical JAK inhibitor was considered to be a clinically meaningful, not just significant from a statistical standpoint.

In fact, improvement on the 5-point Vitiligo Noticeability Scale “also supported a clinically meaningful benefit,” Dr. Rosmarin reported. When those achieving a score of 4 (much less noticeable) or 5 (no longer noticeable), the response rates at 24 weeks were 24.5% and 21.6% in the TRuE-V1 and TRuE-V2 trials, respectively. Again, these response rates were several times greater than the 3.3% (P < .001) and 6.6% (P < .01) observed in the vehicle arms of TRuE-V1 and TRuE-V2 (P < .01), respectively.

Treatment-related adverse events were infrequent. The most common were acne at the application site, which occurred in about 5% of patients receiving ruxolitinib (vs. 2% or fewer of those receiving vehicle) and pruritus, which also occurred in about 5% of patients. However, the rates of pruritus among those on placebo reached 4% in TRuE-V1 and 2% in TRuE-V2 trials.

In vitiligo, where there has been recent progress in understanding the pathophysiology, loss of melanocytes in immune dysregulation has been linked to activation of the JAK signaling pathway, according to Dr. Rosmarin. In the 52-week phase 2 trial with 205 patients, ruxolitinib was associated with a sustained response and no serious treatment-related adverse events.
 

52-week data might show more benefit

Patients are continuing to be followed in the TRuE-V1 and TRuE-V-2 trials. Based on the phase 2 data and on the progressive improvement still being observed at the end of 24 weeks in the phase 3 trials, Dr. Rosmarin expects 52-week results be valuable in understanding the clinical role of ruxolitinib.

“We will be looking for further improvement in response as we follow these patients out to 1 year,” he said.

This further follow-up is important, agreed Iltefat Hamzavi, MD, senior staff physician, department of dermatology, Henry Ford Hospital, Detroit.

Despite the promise of perhaps other JAK inhibitors, “we still need to understand how long it will take for the drug to offer optimal results. We already know that is more than 24 weeks,” said Dr. Hamzavi, who has been involved in the clinical trials with this drug but was not involved with the TRuE-V1 or -V2 trials.

He also said more follow-up is needed to understand the duration of effect. He is, however, optimistic about the clinical role of this mechanism for treatment of vitiligo.

“I do think that JAK inhibitors show a lot of promise [in vitiligo] for certain locations of the body,” he said.

Given the limited treatment options for effective and prolonged improvement in vitiligo, both Dr. Hamzavi and Dr. Rosmarin indicated an effective topical cream is likely to be considered by physicians and patients to be a substantial advance.

On Sept. 21, ruxolitinib (Opzelura) 1.5% cream was approved by the Food and Drug Administration for the short-term treatment of mild to moderate atopic dermatitis in children and adults ages 12 years and older – the first FDA approval of this product.

Dr. Rosmarin reported financial relationships with more than 20 pharmaceutical companies, including Incyte, which provided funding for the TRuE-V1 and -V2 trials. Dr. Hamzavi reported financial relationships with more than 15 companies with pharmaceutical or cosmetic products, including Incyte.

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

A topical cream formulation of the Janus kinase inhibitor ruxolitinib was superior to its vehicle for treating vitiligo across all primary and secondary endpoints in two multicenter phase 3 trials presented together at the annual meeting of the European Academy of Dermatology and Venereology.

On the primary endpoint of F-VASI 75 (75% improvement in the Facial and Vitiligo Scoring Index), rates were nearly four times higher at 24 weeks in one trial (29.9% vs. 7.5%; P < .0001) and more than twice as great in the other (29.9% vs. 12.9%; P < .01).

“The larger phase 3 trials confirm the previous phase 2 findings,” reported David Rosmarin, MD, vice chairman for research and education, department of dermatology, Tufts Medical Center, Boston. These findings not only include substantial clinical efficacy but good tolerability with “no serious treatment-related adverse events,” he noted.
 

600 patients randomized

In one of the trials, called TRuE-V1, 330 patients with vitiligo were randomly assigned in a 2:1 ratio to 1.5% ruxolitinib or vehicle applied twice daily. In the other trial, called TRuE-V2, 344 patients were randomly assigned. The participating centers were in Europe and North America.

Patients aged 12 years or older with nonsegmental vitiligo and depigmentation covering no more than 10% of the total body surface area were eligible. The mean baseline F-VASI values were 1.0. The mean total VASI (T-FASI) values were 6.5. On those enrolled, half were female, 11% were adolescents, and 73% had Fitzpatrick skin phototypes III-VI.

Ruxolitinib cream provided near-complete vitiligo clearance (F-VASI 90) on the face at 24 weeks in only about 15% of patients, but this was several times higher than the 2% achieved on vehicle in the TRuE-V1 (P < .01) and the TRuE-V2 trials (P < .05), respectively.

F-VASI 50 response rates greater than 50%

For F-VASI 50, the response rate with ruxolitinib in both studies was approximately 51%. Relative to the 17.2% response on vehicle in TRuE-v1 and 23.4% in TRuE-V2 (both P < .0001 vs. active therapy), the advantage of the topical JAK inhibitor was considered to be a clinically meaningful, not just significant from a statistical standpoint.

In fact, improvement on the 5-point Vitiligo Noticeability Scale “also supported a clinically meaningful benefit,” Dr. Rosmarin reported. When those achieving a score of 4 (much less noticeable) or 5 (no longer noticeable), the response rates at 24 weeks were 24.5% and 21.6% in the TRuE-V1 and TRuE-V2 trials, respectively. Again, these response rates were several times greater than the 3.3% (P < .001) and 6.6% (P < .01) observed in the vehicle arms of TRuE-V1 and TRuE-V2 (P < .01), respectively.

Treatment-related adverse events were infrequent. The most common were acne at the application site, which occurred in about 5% of patients receiving ruxolitinib (vs. 2% or fewer of those receiving vehicle) and pruritus, which also occurred in about 5% of patients. However, the rates of pruritus among those on placebo reached 4% in TRuE-V1 and 2% in TRuE-V2 trials.

In vitiligo, where there has been recent progress in understanding the pathophysiology, loss of melanocytes in immune dysregulation has been linked to activation of the JAK signaling pathway, according to Dr. Rosmarin. In the 52-week phase 2 trial with 205 patients, ruxolitinib was associated with a sustained response and no serious treatment-related adverse events.
 

52-week data might show more benefit

Patients are continuing to be followed in the TRuE-V1 and TRuE-V-2 trials. Based on the phase 2 data and on the progressive improvement still being observed at the end of 24 weeks in the phase 3 trials, Dr. Rosmarin expects 52-week results be valuable in understanding the clinical role of ruxolitinib.

“We will be looking for further improvement in response as we follow these patients out to 1 year,” he said.

This further follow-up is important, agreed Iltefat Hamzavi, MD, senior staff physician, department of dermatology, Henry Ford Hospital, Detroit.

Despite the promise of perhaps other JAK inhibitors, “we still need to understand how long it will take for the drug to offer optimal results. We already know that is more than 24 weeks,” said Dr. Hamzavi, who has been involved in the clinical trials with this drug but was not involved with the TRuE-V1 or -V2 trials.

He also said more follow-up is needed to understand the duration of effect. He is, however, optimistic about the clinical role of this mechanism for treatment of vitiligo.

“I do think that JAK inhibitors show a lot of promise [in vitiligo] for certain locations of the body,” he said.

Given the limited treatment options for effective and prolonged improvement in vitiligo, both Dr. Hamzavi and Dr. Rosmarin indicated an effective topical cream is likely to be considered by physicians and patients to be a substantial advance.

On Sept. 21, ruxolitinib (Opzelura) 1.5% cream was approved by the Food and Drug Administration for the short-term treatment of mild to moderate atopic dermatitis in children and adults ages 12 years and older – the first FDA approval of this product.

Dr. Rosmarin reported financial relationships with more than 20 pharmaceutical companies, including Incyte, which provided funding for the TRuE-V1 and -V2 trials. Dr. Hamzavi reported financial relationships with more than 15 companies with pharmaceutical or cosmetic products, including Incyte.

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

One of the most commonly used organic acids used on the skin, lactic acid, has been used for over 3 decades. Originally derived from milk or plant-derived sugars, this gentle exfoliating acid can be used in peels, serums, masks, and toners, and has the additional benefit of hydrating the skin. Lactic acid is formulated in concentrations from 2% to 50%; however, because of its large molecular size, it doesn’t penetrate the deeper layers of the dermis to the same extent as the other alpha-hydroxy acids (AHAs), such as glycolic acid. Thus, it is one of the gentler exfoliants and one that can be used in sensitive skin or darker skin types.

Similar to other AHAs, lactic acid is used topically to treat hyperpigmentation, textural abnormalities, acne scars, enlarged pores, and acne. Despite its mild peeling effects, lactic acid is best used to treat xerotic skin because of its function as a humectant, drawing moisture into the stratum corneum. Similar to the other AHAs, lactic acid has also been shown to decrease melanogenesis and is a gentle treatment for skin hyperpigmentation, particularly in skin of color. Side effects include peeling, stinging, erythema, photosensitivity, and hyperpigmentation when improperly used.

Very little clinical research has been reported in the last 20 years as to the uses and benefits of lactic acid in skincare. In my clinical experience, daily use of lactic acid is more effective and has more long-term benefits for hydration and rejuvenation of the skin than the other AHAs. Concentrations of 10%-15% used daily on the skin as a mild exfoliant and humectant have shown to improve texture, decrease pigmentation and improve fine lines – without thinning of the skin seen with the deeper dermal penetrating acids.

Confusion in the market has also risen as many over-the-counter brands have included ammonium lactate in their portfolio of moisturizers. Ammonium lactate is a combination of ammonium hydroxide and lactic acid, or the salt of lactic acid. A comparative study evaluating the difference between 5% lactic acid and 12% ammonium lactate for the treatment of xerosis showed that ammonium lactate was significantly more effective at reducing xerosis. It is widely used in the treatment of keratosis pilaris, calluses, xerosis, and ichthyosis.

Widespread use of lactic acid has not gotten as much glory as that of glycolic acid. However, in clinical practice, its functions are more widespread. It is a much safer acid to use, and its added benefit of increasing hydration of the skin is crucial in its long-term use for both photoaging and the prevention of wrinkles. With any acid, the exfoliating properties must be treated with adequate hydration and barrier repair.

The intrinsic moisturizing effect of lactic acid makes it a much more well-rounded acid and that can be used for longer periods of time in a broader spectrum of patients.

Dr. Lily Talakoub and Dr. Naissan O. Wesley are cocontributors to this column. Dr. Talakoub is in private practice in McLean, Va. Dr. Wesley practices dermatology in Beverly Hills, Calif. This month’s column is by Dr. Talakoub. Write to them at [email protected]. They had no relevant disclosures.

One of the most commonly used organic acids used on the skin, lactic acid, has been used for over 3 decades. Originally derived from milk or plant-derived sugars, this gentle exfoliating acid can be used in peels, serums, masks, and toners, and has the additional benefit of hydrating the skin. Lactic acid is formulated in concentrations from 2% to 50%; however, because of its large molecular size, it doesn’t penetrate the deeper layers of the dermis to the same extent as the other alpha-hydroxy acids (AHAs), such as glycolic acid. Thus, it is one of the gentler exfoliants and one that can be used in sensitive skin or darker skin types.

Similar to other AHAs, lactic acid is used topically to treat hyperpigmentation, textural abnormalities, acne scars, enlarged pores, and acne. Despite its mild peeling effects, lactic acid is best used to treat xerotic skin because of its function as a humectant, drawing moisture into the stratum corneum. Similar to the other AHAs, lactic acid has also been shown to decrease melanogenesis and is a gentle treatment for skin hyperpigmentation, particularly in skin of color. Side effects include peeling, stinging, erythema, photosensitivity, and hyperpigmentation when improperly used.

Very little clinical research has been reported in the last 20 years as to the uses and benefits of lactic acid in skincare. In my clinical experience, daily use of lactic acid is more effective and has more long-term benefits for hydration and rejuvenation of the skin than the other AHAs. Concentrations of 10%-15% used daily on the skin as a mild exfoliant and humectant have shown to improve texture, decrease pigmentation and improve fine lines – without thinning of the skin seen with the deeper dermal penetrating acids.

Confusion in the market has also risen as many over-the-counter brands have included ammonium lactate in their portfolio of moisturizers. Ammonium lactate is a combination of ammonium hydroxide and lactic acid, or the salt of lactic acid. A comparative study evaluating the difference between 5% lactic acid and 12% ammonium lactate for the treatment of xerosis showed that ammonium lactate was significantly more effective at reducing xerosis. It is widely used in the treatment of keratosis pilaris, calluses, xerosis, and ichthyosis.

Widespread use of lactic acid has not gotten as much glory as that of glycolic acid. However, in clinical practice, its functions are more widespread. It is a much safer acid to use, and its added benefit of increasing hydration of the skin is crucial in its long-term use for both photoaging and the prevention of wrinkles. With any acid, the exfoliating properties must be treated with adequate hydration and barrier repair.

The intrinsic moisturizing effect of lactic acid makes it a much more well-rounded acid and that can be used for longer periods of time in a broader spectrum of patients.

Dr. Lily Talakoub and Dr. Naissan O. Wesley are cocontributors to this column. Dr. Talakoub is in private practice in McLean, Va. Dr. Wesley practices dermatology in Beverly Hills, Calif. This month’s column is by Dr. Talakoub. Write to them at [email protected]. They had no relevant disclosures.

One of the most commonly used organic acids used on the skin, lactic acid, has been used for over 3 decades. Originally derived from milk or plant-derived sugars, this gentle exfoliating acid can be used in peels, serums, masks, and toners, and has the additional benefit of hydrating the skin. Lactic acid is formulated in concentrations from 2% to 50%; however, because of its large molecular size, it doesn’t penetrate the deeper layers of the dermis to the same extent as the other alpha-hydroxy acids (AHAs), such as glycolic acid. Thus, it is one of the gentler exfoliants and one that can be used in sensitive skin or darker skin types.

Similar to other AHAs, lactic acid is used topically to treat hyperpigmentation, textural abnormalities, acne scars, enlarged pores, and acne. Despite its mild peeling effects, lactic acid is best used to treat xerotic skin because of its function as a humectant, drawing moisture into the stratum corneum. Similar to the other AHAs, lactic acid has also been shown to decrease melanogenesis and is a gentle treatment for skin hyperpigmentation, particularly in skin of color. Side effects include peeling, stinging, erythema, photosensitivity, and hyperpigmentation when improperly used.

Very little clinical research has been reported in the last 20 years as to the uses and benefits of lactic acid in skincare. In my clinical experience, daily use of lactic acid is more effective and has more long-term benefits for hydration and rejuvenation of the skin than the other AHAs. Concentrations of 10%-15% used daily on the skin as a mild exfoliant and humectant have shown to improve texture, decrease pigmentation and improve fine lines – without thinning of the skin seen with the deeper dermal penetrating acids.

Confusion in the market has also risen as many over-the-counter brands have included ammonium lactate in their portfolio of moisturizers. Ammonium lactate is a combination of ammonium hydroxide and lactic acid, or the salt of lactic acid. A comparative study evaluating the difference between 5% lactic acid and 12% ammonium lactate for the treatment of xerosis showed that ammonium lactate was significantly more effective at reducing xerosis. It is widely used in the treatment of keratosis pilaris, calluses, xerosis, and ichthyosis.

Widespread use of lactic acid has not gotten as much glory as that of glycolic acid. However, in clinical practice, its functions are more widespread. It is a much safer acid to use, and its added benefit of increasing hydration of the skin is crucial in its long-term use for both photoaging and the prevention of wrinkles. With any acid, the exfoliating properties must be treated with adequate hydration and barrier repair.

The intrinsic moisturizing effect of lactic acid makes it a much more well-rounded acid and that can be used for longer periods of time in a broader spectrum of patients.

Dr. Lily Talakoub and Dr. Naissan O. Wesley are cocontributors to this column. Dr. Talakoub is in private practice in McLean, Va. Dr. Wesley practices dermatology in Beverly Hills, Calif. This month’s column is by Dr. Talakoub. Write to them at [email protected]. They had no relevant disclosures.

Health insurance coverage policies for vitiligo treatment lack uniformity and are marked by significant gaps in coverage, which may disproportionately affect patients of color.

MarijaRadovic/Getty Images

Those are the conclusions from an analysis of vitiligo treatment coverage policies across major health insurers in the United States.

“Vitiligo can be less noticeable in patients with lighter skin types, becoming apparent only when affected patches fail to tan,” first authors Andrew Blundell, MD, MSc, and Moniyka Sachar, MD, wrote in a study published online on July 16 in Pediatric Dermatology. However, they pointed out that, in patients with darker skin types, “vitiligo can be far more evident due to the stark contrast of involved versus uninvolved skin, and as such can lead to a significant impact on quality of life, as well as heightened stigmatization.”

Nevertheless, they noted many health care insurers consider vitiligo as a cosmetic condition, and do not cover treatments, and for the 1%-2% of the general population with vitiligo, “this lack of recognition from health care insurers makes treatments both less accessible and affordable, and only further marginalizes patients with this condition.”

Dr. Blundell, of San Juan Bautista School of Medicine, Caguas, P.R., and Dr. Sachar, of the department of dermatology at Brown University, Providence, R.I., and colleagues surveyed 15 commercial health care insurers, 50 BlueCross BlueShield plans, Medicare, Medicaid, and Veterans Affairs to determine the level of treatment coverage for vitiligo. They looked at office visits, medications (the topical calcineurin inhibitors [TCIs] pimecrolimus, and tacrolimus), excimer laser therapy, and phototherapy (psoralen with UVA [PUVA] and narrow-band UVB [nbUVB]). They collected information from medical policies available online or by direct contact with the plans in 2018.

The researchers reported data from 17 organizations with regional or national coverage policies for vitiligo treatment and two others – BlueCross BlueShield and Medicaid – which had policies that differed by state and plan. Of the 17 organizations, only 12% did not cover TCIs, 56% did not cover nbUVB phototherapy, 53% did not cover PUVA phototherapy, and 41% did not cover laser therapy.

As for BlueCross BlueShield, the health plan did not cover pimecrolimus and tacrolimus in 39% and 35% of states, respectively. At the same time, NbUVB and PUVA therapy were not covered in 20% and 10% of states, respectively, while excimer laser therapy was not covered in 82% of states.

Of accessible Medicaid information from 32 states, 11 did not cover topicals, 5 did not cover nbUVB, 4 did not cover PUVA, and 7 did not cover laser therapy. “The two most commonly cited reasons for denial of coverage were (a) vitiligo is considered a cosmetic condition and (b) certain therapies are not FDA-approved for vitiligo, though they may be approved for other skin conditions,” the study authors wrote.

While the analysis revealed that topical TCI therapy is more widely covered by insurance companies, compared with phototherapy, “multiple studies have shown that a combination of both topical and phototherapy is more effective in treating vitiligo than either alone,” they noted. “Vitiligo treatments can delay the progression of the disease and result in better outcomes when started early, furthering the need for insurance coverage of these treatments. If all proven and accepted vitiligo treatments were covered by their health insurers, patients would have better access, as well as timely and affordable ways by which to limit depigmentation and to repigment affected areas.”

In addition, lack of access to treatments “may increase health disparities among already-marginalized groups, such as children and adults of darker skin phototypes,” they wrote.

[email protected]

Health insurance coverage policies for vitiligo treatment lack uniformity and are marked by significant gaps in coverage, which may disproportionately affect patients of color.

MarijaRadovic/Getty Images

Those are the conclusions from an analysis of vitiligo treatment coverage policies across major health insurers in the United States.

“Vitiligo can be less noticeable in patients with lighter skin types, becoming apparent only when affected patches fail to tan,” first authors Andrew Blundell, MD, MSc, and Moniyka Sachar, MD, wrote in a study published online on July 16 in Pediatric Dermatology. However, they pointed out that, in patients with darker skin types, “vitiligo can be far more evident due to the stark contrast of involved versus uninvolved skin, and as such can lead to a significant impact on quality of life, as well as heightened stigmatization.”

Nevertheless, they noted many health care insurers consider vitiligo as a cosmetic condition, and do not cover treatments, and for the 1%-2% of the general population with vitiligo, “this lack of recognition from health care insurers makes treatments both less accessible and affordable, and only further marginalizes patients with this condition.”

Dr. Blundell, of San Juan Bautista School of Medicine, Caguas, P.R., and Dr. Sachar, of the department of dermatology at Brown University, Providence, R.I., and colleagues surveyed 15 commercial health care insurers, 50 BlueCross BlueShield plans, Medicare, Medicaid, and Veterans Affairs to determine the level of treatment coverage for vitiligo. They looked at office visits, medications (the topical calcineurin inhibitors [TCIs] pimecrolimus, and tacrolimus), excimer laser therapy, and phototherapy (psoralen with UVA [PUVA] and narrow-band UVB [nbUVB]). They collected information from medical policies available online or by direct contact with the plans in 2018.

The researchers reported data from 17 organizations with regional or national coverage policies for vitiligo treatment and two others – BlueCross BlueShield and Medicaid – which had policies that differed by state and plan. Of the 17 organizations, only 12% did not cover TCIs, 56% did not cover nbUVB phototherapy, 53% did not cover PUVA phototherapy, and 41% did not cover laser therapy.

As for BlueCross BlueShield, the health plan did not cover pimecrolimus and tacrolimus in 39% and 35% of states, respectively. At the same time, NbUVB and PUVA therapy were not covered in 20% and 10% of states, respectively, while excimer laser therapy was not covered in 82% of states.

Of accessible Medicaid information from 32 states, 11 did not cover topicals, 5 did not cover nbUVB, 4 did not cover PUVA, and 7 did not cover laser therapy. “The two most commonly cited reasons for denial of coverage were (a) vitiligo is considered a cosmetic condition and (b) certain therapies are not FDA-approved for vitiligo, though they may be approved for other skin conditions,” the study authors wrote.

While the analysis revealed that topical TCI therapy is more widely covered by insurance companies, compared with phototherapy, “multiple studies have shown that a combination of both topical and phototherapy is more effective in treating vitiligo than either alone,” they noted. “Vitiligo treatments can delay the progression of the disease and result in better outcomes when started early, furthering the need for insurance coverage of these treatments. If all proven and accepted vitiligo treatments were covered by their health insurers, patients would have better access, as well as timely and affordable ways by which to limit depigmentation and to repigment affected areas.”

In addition, lack of access to treatments “may increase health disparities among already-marginalized groups, such as children and adults of darker skin phototypes,” they wrote.

[email protected]

Health insurance coverage policies for vitiligo treatment lack uniformity and are marked by significant gaps in coverage, which may disproportionately affect patients of color.

MarijaRadovic/Getty Images

Those are the conclusions from an analysis of vitiligo treatment coverage policies across major health insurers in the United States.

“Vitiligo can be less noticeable in patients with lighter skin types, becoming apparent only when affected patches fail to tan,” first authors Andrew Blundell, MD, MSc, and Moniyka Sachar, MD, wrote in a study published online on July 16 in Pediatric Dermatology. However, they pointed out that, in patients with darker skin types, “vitiligo can be far more evident due to the stark contrast of involved versus uninvolved skin, and as such can lead to a significant impact on quality of life, as well as heightened stigmatization.”

Nevertheless, they noted many health care insurers consider vitiligo as a cosmetic condition, and do not cover treatments, and for the 1%-2% of the general population with vitiligo, “this lack of recognition from health care insurers makes treatments both less accessible and affordable, and only further marginalizes patients with this condition.”

Dr. Blundell, of San Juan Bautista School of Medicine, Caguas, P.R., and Dr. Sachar, of the department of dermatology at Brown University, Providence, R.I., and colleagues surveyed 15 commercial health care insurers, 50 BlueCross BlueShield plans, Medicare, Medicaid, and Veterans Affairs to determine the level of treatment coverage for vitiligo. They looked at office visits, medications (the topical calcineurin inhibitors [TCIs] pimecrolimus, and tacrolimus), excimer laser therapy, and phototherapy (psoralen with UVA [PUVA] and narrow-band UVB [nbUVB]). They collected information from medical policies available online or by direct contact with the plans in 2018.

The researchers reported data from 17 organizations with regional or national coverage policies for vitiligo treatment and two others – BlueCross BlueShield and Medicaid – which had policies that differed by state and plan. Of the 17 organizations, only 12% did not cover TCIs, 56% did not cover nbUVB phototherapy, 53% did not cover PUVA phototherapy, and 41% did not cover laser therapy.

As for BlueCross BlueShield, the health plan did not cover pimecrolimus and tacrolimus in 39% and 35% of states, respectively. At the same time, NbUVB and PUVA therapy were not covered in 20% and 10% of states, respectively, while excimer laser therapy was not covered in 82% of states.

Of accessible Medicaid information from 32 states, 11 did not cover topicals, 5 did not cover nbUVB, 4 did not cover PUVA, and 7 did not cover laser therapy. “The two most commonly cited reasons for denial of coverage were (a) vitiligo is considered a cosmetic condition and (b) certain therapies are not FDA-approved for vitiligo, though they may be approved for other skin conditions,” the study authors wrote.

While the analysis revealed that topical TCI therapy is more widely covered by insurance companies, compared with phototherapy, “multiple studies have shown that a combination of both topical and phototherapy is more effective in treating vitiligo than either alone,” they noted. “Vitiligo treatments can delay the progression of the disease and result in better outcomes when started early, furthering the need for insurance coverage of these treatments. If all proven and accepted vitiligo treatments were covered by their health insurers, patients would have better access, as well as timely and affordable ways by which to limit depigmentation and to repigment affected areas.”

In addition, lack of access to treatments “may increase health disparities among already-marginalized groups, such as children and adults of darker skin phototypes,” they wrote.

[email protected]

When used for appropriate patients, MRI imaging is helpful in congenital melanocytic nevus (CMN) management and may help predict neurologic outcomes or drive neurosurgical intervention, results from a small multi-institutional study showed.

“The majority of congenital nevi are considered low risk for cutaneous and/or systemic complications,” Holly Neale said at the annual meeting of the Society for Pediatric Dermatology. “However, a subset of children born with higher-risk congenital nevi require close monitoring, as some features of congenital nevi have been associated with cutaneous melanoma, central nervous system melanoma, melanin in the brain or spine, and structural irregularities in the brain or spine. It’s important to understand which congenital nevi are considered higher risk in order to guide management and counseling decisions.”

One major management decision is to do a screening magnetic resonance image of the CNS to evaluate for neurologic involvement, said Ms. Neale, a fourth-year medical student at the University of Massachusetts, Worcester. Prior studies have shown that congenital nevi that are bigger than 20 cm, posterior axial location, and having more than one congenital nevus may predict CNS abnormalities, while recent guidelines from experts in the field suggest that any child with more than one congenital nevus at birth undergo screening MRI.

“However, guidelines are evolving, and more data is required to better understand the CNS abnormalities and patient outcomes for children with congenital nevi,” said Ms. Neale, who spent the past year as a pediatric dermatology research fellow at Massachusetts General Hospital, Boston.

To address this knowledge gap, she and colleagues at the University of Massachusetts, Massachusetts General Hospital, and Boston Children’s Hospital performed a retrospective chart review between Jan. 1, 2009, and Dec. 31, 2019, of individuals ages 18 and younger who had an MRI of the brain or spine with at least one dermatologist-diagnosed nevus as identified via key words in the medical record. Of the 909 patients screened, 46 met inclusion criteria, evenly split between males and females.

The most common location of the largest nevus was the trunk (in 41% of patients), followed by lesions that spanned multiple regions. More than one-third of patients had giant nevi (greater than 40 cm).

“The majority of images were considered nonconcerning, which includes normal, benign, or other findings such as trauma related, infectious, or orthopedic, which we did not classify as abnormal as it did not guide our study question,” Ms. Neale said. Specifically, 8% of spine images and 27% of brain images were considered “concerning,” defined as any finding that prompted further workup or monitoring, which includes findings concerning for melanin.

The most common brain finding was melanin (in eight children), and one child with brain melanin also had findings suggestive of melanin in the thoracic spine. The most common finding in spine MRIs was fatty filum (in four children), requiring intervention for tethering in only one individual. No cases of cutaneous melanoma developed during the study period, and only one patient with abnormal imaging had CNS melanoma, which was fatal.

All patients with findings suggestive of CNS melanin had more than four nevi present at birth, which is in line with current imaging screening guidelines. In addition, children with concerning imaging had higher rates of death, neurodevelopmental problems, seizures, and neurosurgery, compared with their counterparts with unremarkable imaging findings. Describing preliminary analyses, Ms. Neale said that a chi square analysis was performed to test statistical significance of these differences, “and neurosurgery was the only variable that children with concerning imaging were significantly more likely to experience, although sample size limits detection for the other variables.”

The authors concluded that MRI is a helpful tool when used in the appropriate clinical context for the management of congenital nevi. “As more children undergo imaging, we may discover more nonmelanin abnormalities,” she said.

Joseph M. Lam, MD, who was asked to comment on the study, said that the increased risk of CNS melanin in patients with larger lesions and in those with multiple lesions confirms previous reports.

“It is interesting to note that some patients with nonconcerning imaging results still had neurodevelopmental problems and seizures, albeit at a lower rate than those with concerning imaging results,” said Dr. Lam, a pediatric dermatologist at British Columbia Children’s Hospital, Vancouver. “The lack of a control group for comparison of rates of neurological sequelae, such as NDP, seizures and nonmelanin structural anomalies, limits the generalizability of the findings. However, this is a nice study that helps us understand better the CNS anomalies in CMN.”

Ms. Neale acknowledged certain limitations of the study, including the lack of a control group without CMN, the small number of patients, the potential for referral bias, and its retrospective design. Also, the proximity of the study period does not allow for chronic follow-up and detection of the development of melanoma or other problems in the future.

Ms. Neale and associates reported having no relevant financial disclosures. Dr. Lam disclosed that he has received speaker fees from Pierre Fabre.

[email protected]

When used for appropriate patients, MRI imaging is helpful in congenital melanocytic nevus (CMN) management and may help predict neurologic outcomes or drive neurosurgical intervention, results from a small multi-institutional study showed.

“The majority of congenital nevi are considered low risk for cutaneous and/or systemic complications,” Holly Neale said at the annual meeting of the Society for Pediatric Dermatology. “However, a subset of children born with higher-risk congenital nevi require close monitoring, as some features of congenital nevi have been associated with cutaneous melanoma, central nervous system melanoma, melanin in the brain or spine, and structural irregularities in the brain or spine. It’s important to understand which congenital nevi are considered higher risk in order to guide management and counseling decisions.”

One major management decision is to do a screening magnetic resonance image of the CNS to evaluate for neurologic involvement, said Ms. Neale, a fourth-year medical student at the University of Massachusetts, Worcester. Prior studies have shown that congenital nevi that are bigger than 20 cm, posterior axial location, and having more than one congenital nevus may predict CNS abnormalities, while recent guidelines from experts in the field suggest that any child with more than one congenital nevus at birth undergo screening MRI.

“However, guidelines are evolving, and more data is required to better understand the CNS abnormalities and patient outcomes for children with congenital nevi,” said Ms. Neale, who spent the past year as a pediatric dermatology research fellow at Massachusetts General Hospital, Boston.

To address this knowledge gap, she and colleagues at the University of Massachusetts, Massachusetts General Hospital, and Boston Children’s Hospital performed a retrospective chart review between Jan. 1, 2009, and Dec. 31, 2019, of individuals ages 18 and younger who had an MRI of the brain or spine with at least one dermatologist-diagnosed nevus as identified via key words in the medical record. Of the 909 patients screened, 46 met inclusion criteria, evenly split between males and females.

The most common location of the largest nevus was the trunk (in 41% of patients), followed by lesions that spanned multiple regions. More than one-third of patients had giant nevi (greater than 40 cm).

“The majority of images were considered nonconcerning, which includes normal, benign, or other findings such as trauma related, infectious, or orthopedic, which we did not classify as abnormal as it did not guide our study question,” Ms. Neale said. Specifically, 8% of spine images and 27% of brain images were considered “concerning,” defined as any finding that prompted further workup or monitoring, which includes findings concerning for melanin.

The most common brain finding was melanin (in eight children), and one child with brain melanin also had findings suggestive of melanin in the thoracic spine. The most common finding in spine MRIs was fatty filum (in four children), requiring intervention for tethering in only one individual. No cases of cutaneous melanoma developed during the study period, and only one patient with abnormal imaging had CNS melanoma, which was fatal.

All patients with findings suggestive of CNS melanin had more than four nevi present at birth, which is in line with current imaging screening guidelines. In addition, children with concerning imaging had higher rates of death, neurodevelopmental problems, seizures, and neurosurgery, compared with their counterparts with unremarkable imaging findings. Describing preliminary analyses, Ms. Neale said that a chi square analysis was performed to test statistical significance of these differences, “and neurosurgery was the only variable that children with concerning imaging were significantly more likely to experience, although sample size limits detection for the other variables.”

The authors concluded that MRI is a helpful tool when used in the appropriate clinical context for the management of congenital nevi. “As more children undergo imaging, we may discover more nonmelanin abnormalities,” she said.

Joseph M. Lam, MD, who was asked to comment on the study, said that the increased risk of CNS melanin in patients with larger lesions and in those with multiple lesions confirms previous reports.

“It is interesting to note that some patients with nonconcerning imaging results still had neurodevelopmental problems and seizures, albeit at a lower rate than those with concerning imaging results,” said Dr. Lam, a pediatric dermatologist at British Columbia Children’s Hospital, Vancouver. “The lack of a control group for comparison of rates of neurological sequelae, such as NDP, seizures and nonmelanin structural anomalies, limits the generalizability of the findings. However, this is a nice study that helps us understand better the CNS anomalies in CMN.”

Ms. Neale acknowledged certain limitations of the study, including the lack of a control group without CMN, the small number of patients, the potential for referral bias, and its retrospective design. Also, the proximity of the study period does not allow for chronic follow-up and detection of the development of melanoma or other problems in the future.

Ms. Neale and associates reported having no relevant financial disclosures. Dr. Lam disclosed that he has received speaker fees from Pierre Fabre.

[email protected]

When used for appropriate patients, MRI imaging is helpful in congenital melanocytic nevus (CMN) management and may help predict neurologic outcomes or drive neurosurgical intervention, results from a small multi-institutional study showed.

“The majority of congenital nevi are considered low risk for cutaneous and/or systemic complications,” Holly Neale said at the annual meeting of the Society for Pediatric Dermatology. “However, a subset of children born with higher-risk congenital nevi require close monitoring, as some features of congenital nevi have been associated with cutaneous melanoma, central nervous system melanoma, melanin in the brain or spine, and structural irregularities in the brain or spine. It’s important to understand which congenital nevi are considered higher risk in order to guide management and counseling decisions.”

One major management decision is to do a screening magnetic resonance image of the CNS to evaluate for neurologic involvement, said Ms. Neale, a fourth-year medical student at the University of Massachusetts, Worcester. Prior studies have shown that congenital nevi that are bigger than 20 cm, posterior axial location, and having more than one congenital nevus may predict CNS abnormalities, while recent guidelines from experts in the field suggest that any child with more than one congenital nevus at birth undergo screening MRI.

“However, guidelines are evolving, and more data is required to better understand the CNS abnormalities and patient outcomes for children with congenital nevi,” said Ms. Neale, who spent the past year as a pediatric dermatology research fellow at Massachusetts General Hospital, Boston.

To address this knowledge gap, she and colleagues at the University of Massachusetts, Massachusetts General Hospital, and Boston Children’s Hospital performed a retrospective chart review between Jan. 1, 2009, and Dec. 31, 2019, of individuals ages 18 and younger who had an MRI of the brain or spine with at least one dermatologist-diagnosed nevus as identified via key words in the medical record. Of the 909 patients screened, 46 met inclusion criteria, evenly split between males and females.

The most common location of the largest nevus was the trunk (in 41% of patients), followed by lesions that spanned multiple regions. More than one-third of patients had giant nevi (greater than 40 cm).

“The majority of images were considered nonconcerning, which includes normal, benign, or other findings such as trauma related, infectious, or orthopedic, which we did not classify as abnormal as it did not guide our study question,” Ms. Neale said. Specifically, 8% of spine images and 27% of brain images were considered “concerning,” defined as any finding that prompted further workup or monitoring, which includes findings concerning for melanin.

The most common brain finding was melanin (in eight children), and one child with brain melanin also had findings suggestive of melanin in the thoracic spine. The most common finding in spine MRIs was fatty filum (in four children), requiring intervention for tethering in only one individual. No cases of cutaneous melanoma developed during the study period, and only one patient with abnormal imaging had CNS melanoma, which was fatal.

All patients with findings suggestive of CNS melanin had more than four nevi present at birth, which is in line with current imaging screening guidelines. In addition, children with concerning imaging had higher rates of death, neurodevelopmental problems, seizures, and neurosurgery, compared with their counterparts with unremarkable imaging findings. Describing preliminary analyses, Ms. Neale said that a chi square analysis was performed to test statistical significance of these differences, “and neurosurgery was the only variable that children with concerning imaging were significantly more likely to experience, although sample size limits detection for the other variables.”

The authors concluded that MRI is a helpful tool when used in the appropriate clinical context for the management of congenital nevi. “As more children undergo imaging, we may discover more nonmelanin abnormalities,” she said.

Joseph M. Lam, MD, who was asked to comment on the study, said that the increased risk of CNS melanin in patients with larger lesions and in those with multiple lesions confirms previous reports.

“It is interesting to note that some patients with nonconcerning imaging results still had neurodevelopmental problems and seizures, albeit at a lower rate than those with concerning imaging results,” said Dr. Lam, a pediatric dermatologist at British Columbia Children’s Hospital, Vancouver. “The lack of a control group for comparison of rates of neurological sequelae, such as NDP, seizures and nonmelanin structural anomalies, limits the generalizability of the findings. However, this is a nice study that helps us understand better the CNS anomalies in CMN.”

Ms. Neale acknowledged certain limitations of the study, including the lack of a control group without CMN, the small number of patients, the potential for referral bias, and its retrospective design. Also, the proximity of the study period does not allow for chronic follow-up and detection of the development of melanoma or other problems in the future.

Ms. Neale and associates reported having no relevant financial disclosures. Dr. Lam disclosed that he has received speaker fees from Pierre Fabre.

[email protected]

Compared with oral propranolol for the treatment of infantile hemangiomas, oral nadolol resulted in faster and greater size involution and color resolution with a similar safety profile out to 52 weeks, results from a prospective analysis of 71 patients showed.

“In clinical practice, we notice that nadolol works very well in terms of controlling the size and the appearance of the hemangioma,” lead study author Elena Pope, MD, MSc, said during the annual meeting of the Society for Pediatric Dermatology. Hence, she and her colleagues were interested in comparing their clinical experience with the standard treatment with propranolol, and designed a prospective, randomized, controlled, double-blinded study, with the aim of proving that “nadolol is noninferior to propranolol, with a margin of noninferiority of 10%.”

Between 2016 and 2020, Dr. Pope and colleagues at two academic Canadian pediatric dermatology centers enrolled 71 infants aged 1-6 months with significant hemangioma that had either the potential for functional impairment or cosmetic deformity, defined as a lesion greater than 1.5 cm on the face or greater than 3 cm on another body part. Treatment consisted of oral propranolol or nadolol in escalating doses up to 2 mg/kg per day. “The blinding portion of the study was for 24 weeks with a follow-up up to 52 weeks,” said Dr. Pope, professor of pediatrics at the University of Toronto and section head of pediatric dermatology at The Hospital for Sick Children, also in Toronto. “After the unblinding at 24 weeks, patients were allowed to switch their intervention if they were not happy with the results.”

Of the 71 patients, 35 received nadolol and 36 received propranolol. The two groups were similar in terms of clinical and demographic characteristics. Their mean age at enrollment was 3.15 months, 80% were female, 61% were White, 20% were Asian, and the rest were from other ethnic backgrounds.

At 24 weeks, the researchers found that the mean size involution was 97.94% in the nadolol group and 89.14% in the propranolol group (P = .005), while the mean color fading on the visual analogue scale (VAS) was 94.47% in the nadolol group and 80.54% in the propranolol group (P < .001). At 52 weeks, the mean size involution was 99.63% in the nadolol group and 93.63% in the propranolol group (P = .001), while the mean VAS color fading was 97.34% in the nadolol group and 87.23% in the propranolol group (P = .001).

According to Dr. Pope, Kaplan-Meir analysis showed that patients in the propranolol group responded slower to treatment (P = .019), while safety data was similar between the two groups. For example, between weeks 25 and 52, 84.2% of patients in the nadolol group experienced an adverse event, compared with 74.2% of patients in the propranolol group (P = .466). The most common respiratory adverse event was upper respiratory tract infection, which affected 87.5% of patients in the nadolol group, compared with 100% of patients in the propranolol group (P = 0.341).

The most common gastrointestinal adverse event was diarrhea, which affected 66.7% of patients in both groups. One patient in the propranolol group was admitted to the hospital with pneumonia and fully recovered. The incident was not suspected to be related to the medication.

“We believe that this data backs up our clinical experience and it may offer an alternative treatment in other centers where patients experience propranolol unresponsiveness, side effects, or intolerance, or where a fast response is needed,” Dr. Pope said. As for the potential cost implications, “nadolol is cheaper than the Hemangiol but comparable with the compounded formulation of propranolol.”

Concern over the safety of nadolol was raised in a case report published in Pediatrics in 2020. Authors from Alberta reported the case of a 10-week-old girl who was started on nadolol for infantile hemangioma, died 7 weeks later, and was found to have an elevated postmortem cardiac blood nadolol level of 0.94 mg/L. “The infant had no bowel movements for 10 days before her death, which we hypothesize contributed to nadolol toxicity,” the authors wrote.

In a reply to the authors in the same issue of Pediatrics, Dr. Pope, Cathryn Sibbald, MD, and Erin Chung, PhD, pointed out that postmortem redistribution of medications “is complex and measured postmortem cardiac blood concentrations may be significantly higher than the true blood nadolol concentration at the time of death due to significant diffusion from the peripheral tissues.”

They added that the report did not address “other potential errors such as in compounding, dispensing, and administration of the solution,” they wrote, adding: “Finally, we are aware of a Canadian case of death in an infant receiving propranolol, although the cause of death in that case was unable to be determined (ISMP Canada 2016 Safety Bulletin).We agree with the authors that careful consideration of the risks and benefits of beta-blocker therapy should be employed, parents need to be informed when to discontinue therapy and that further research into the pharmacokinetics and pharmacogenetics of beta-blockers are warranted.”

Following publication of the case report in Pediatrics, Dr. Pope said that the only change she made in her practice was to ask families to temporarily discontinue nadolol if their child had constipation for more than 5 days.

The study was supported by a grant from Physician Services, Inc. Dr. Pope reported having no financial disclosures.

[email protected]

Compared with oral propranolol for the treatment of infantile hemangiomas, oral nadolol resulted in faster and greater size involution and color resolution with a similar safety profile out to 52 weeks, results from a prospective analysis of 71 patients showed.

“In clinical practice, we notice that nadolol works very well in terms of controlling the size and the appearance of the hemangioma,” lead study author Elena Pope, MD, MSc, said during the annual meeting of the Society for Pediatric Dermatology. Hence, she and her colleagues were interested in comparing their clinical experience with the standard treatment with propranolol, and designed a prospective, randomized, controlled, double-blinded study, with the aim of proving that “nadolol is noninferior to propranolol, with a margin of noninferiority of 10%.”

Between 2016 and 2020, Dr. Pope and colleagues at two academic Canadian pediatric dermatology centers enrolled 71 infants aged 1-6 months with significant hemangioma that had either the potential for functional impairment or cosmetic deformity, defined as a lesion greater than 1.5 cm on the face or greater than 3 cm on another body part. Treatment consisted of oral propranolol or nadolol in escalating doses up to 2 mg/kg per day. “The blinding portion of the study was for 24 weeks with a follow-up up to 52 weeks,” said Dr. Pope, professor of pediatrics at the University of Toronto and section head of pediatric dermatology at The Hospital for Sick Children, also in Toronto. “After the unblinding at 24 weeks, patients were allowed to switch their intervention if they were not happy with the results.”

Of the 71 patients, 35 received nadolol and 36 received propranolol. The two groups were similar in terms of clinical and demographic characteristics. Their mean age at enrollment was 3.15 months, 80% were female, 61% were White, 20% were Asian, and the rest were from other ethnic backgrounds.

At 24 weeks, the researchers found that the mean size involution was 97.94% in the nadolol group and 89.14% in the propranolol group (P = .005), while the mean color fading on the visual analogue scale (VAS) was 94.47% in the nadolol group and 80.54% in the propranolol group (P < .001). At 52 weeks, the mean size involution was 99.63% in the nadolol group and 93.63% in the propranolol group (P = .001), while the mean VAS color fading was 97.34% in the nadolol group and 87.23% in the propranolol group (P = .001).

According to Dr. Pope, Kaplan-Meir analysis showed that patients in the propranolol group responded slower to treatment (P = .019), while safety data was similar between the two groups. For example, between weeks 25 and 52, 84.2% of patients in the nadolol group experienced an adverse event, compared with 74.2% of patients in the propranolol group (P = .466). The most common respiratory adverse event was upper respiratory tract infection, which affected 87.5% of patients in the nadolol group, compared with 100% of patients in the propranolol group (P = 0.341).

The most common gastrointestinal adverse event was diarrhea, which affected 66.7% of patients in both groups. One patient in the propranolol group was admitted to the hospital with pneumonia and fully recovered. The incident was not suspected to be related to the medication.

“We believe that this data backs up our clinical experience and it may offer an alternative treatment in other centers where patients experience propranolol unresponsiveness, side effects, or intolerance, or where a fast response is needed,” Dr. Pope said. As for the potential cost implications, “nadolol is cheaper than the Hemangiol but comparable with the compounded formulation of propranolol.”

Concern over the safety of nadolol was raised in a case report published in Pediatrics in 2020. Authors from Alberta reported the case of a 10-week-old girl who was started on nadolol for infantile hemangioma, died 7 weeks later, and was found to have an elevated postmortem cardiac blood nadolol level of 0.94 mg/L. “The infant had no bowel movements for 10 days before her death, which we hypothesize contributed to nadolol toxicity,” the authors wrote.

In a reply to the authors in the same issue of Pediatrics, Dr. Pope, Cathryn Sibbald, MD, and Erin Chung, PhD, pointed out that postmortem redistribution of medications “is complex and measured postmortem cardiac blood concentrations may be significantly higher than the true blood nadolol concentration at the time of death due to significant diffusion from the peripheral tissues.”

They added that the report did not address “other potential errors such as in compounding, dispensing, and administration of the solution,” they wrote, adding: “Finally, we are aware of a Canadian case of death in an infant receiving propranolol, although the cause of death in that case was unable to be determined (ISMP Canada 2016 Safety Bulletin).We agree with the authors that careful consideration of the risks and benefits of beta-blocker therapy should be employed, parents need to be informed when to discontinue therapy and that further research into the pharmacokinetics and pharmacogenetics of beta-blockers are warranted.”

Following publication of the case report in Pediatrics, Dr. Pope said that the only change she made in her practice was to ask families to temporarily discontinue nadolol if their child had constipation for more than 5 days.

The study was supported by a grant from Physician Services, Inc. Dr. Pope reported having no financial disclosures.

[email protected]

Compared with oral propranolol for the treatment of infantile hemangiomas, oral nadolol resulted in faster and greater size involution and color resolution with a similar safety profile out to 52 weeks, results from a prospective analysis of 71 patients showed.

“In clinical practice, we notice that nadolol works very well in terms of controlling the size and the appearance of the hemangioma,” lead study author Elena Pope, MD, MSc, said during the annual meeting of the Society for Pediatric Dermatology. Hence, she and her colleagues were interested in comparing their clinical experience with the standard treatment with propranolol, and designed a prospective, randomized, controlled, double-blinded study, with the aim of proving that “nadolol is noninferior to propranolol, with a margin of noninferiority of 10%.”

Between 2016 and 2020, Dr. Pope and colleagues at two academic Canadian pediatric dermatology centers enrolled 71 infants aged 1-6 months with significant hemangioma that had either the potential for functional impairment or cosmetic deformity, defined as a lesion greater than 1.5 cm on the face or greater than 3 cm on another body part. Treatment consisted of oral propranolol or nadolol in escalating doses up to 2 mg/kg per day. “The blinding portion of the study was for 24 weeks with a follow-up up to 52 weeks,” said Dr. Pope, professor of pediatrics at the University of Toronto and section head of pediatric dermatology at The Hospital for Sick Children, also in Toronto. “After the unblinding at 24 weeks, patients were allowed to switch their intervention if they were not happy with the results.”

Of the 71 patients, 35 received nadolol and 36 received propranolol. The two groups were similar in terms of clinical and demographic characteristics. Their mean age at enrollment was 3.15 months, 80% were female, 61% were White, 20% were Asian, and the rest were from other ethnic backgrounds.

At 24 weeks, the researchers found that the mean size involution was 97.94% in the nadolol group and 89.14% in the propranolol group (P = .005), while the mean color fading on the visual analogue scale (VAS) was 94.47% in the nadolol group and 80.54% in the propranolol group (P < .001). At 52 weeks, the mean size involution was 99.63% in the nadolol group and 93.63% in the propranolol group (P = .001), while the mean VAS color fading was 97.34% in the nadolol group and 87.23% in the propranolol group (P = .001).

According to Dr. Pope, Kaplan-Meir analysis showed that patients in the propranolol group responded slower to treatment (P = .019), while safety data was similar between the two groups. For example, between weeks 25 and 52, 84.2% of patients in the nadolol group experienced an adverse event, compared with 74.2% of patients in the propranolol group (P = .466). The most common respiratory adverse event was upper respiratory tract infection, which affected 87.5% of patients in the nadolol group, compared with 100% of patients in the propranolol group (P = 0.341).

The most common gastrointestinal adverse event was diarrhea, which affected 66.7% of patients in both groups. One patient in the propranolol group was admitted to the hospital with pneumonia and fully recovered. The incident was not suspected to be related to the medication.

“We believe that this data backs up our clinical experience and it may offer an alternative treatment in other centers where patients experience propranolol unresponsiveness, side effects, or intolerance, or where a fast response is needed,” Dr. Pope said. As for the potential cost implications, “nadolol is cheaper than the Hemangiol but comparable with the compounded formulation of propranolol.”

Concern over the safety of nadolol was raised in a case report published in Pediatrics in 2020. Authors from Alberta reported the case of a 10-week-old girl who was started on nadolol for infantile hemangioma, died 7 weeks later, and was found to have an elevated postmortem cardiac blood nadolol level of 0.94 mg/L. “The infant had no bowel movements for 10 days before her death, which we hypothesize contributed to nadolol toxicity,” the authors wrote.

In a reply to the authors in the same issue of Pediatrics, Dr. Pope, Cathryn Sibbald, MD, and Erin Chung, PhD, pointed out that postmortem redistribution of medications “is complex and measured postmortem cardiac blood concentrations may be significantly higher than the true blood nadolol concentration at the time of death due to significant diffusion from the peripheral tissues.”

They added that the report did not address “other potential errors such as in compounding, dispensing, and administration of the solution,” they wrote, adding: “Finally, we are aware of a Canadian case of death in an infant receiving propranolol, although the cause of death in that case was unable to be determined (ISMP Canada 2016 Safety Bulletin).We agree with the authors that careful consideration of the risks and benefits of beta-blocker therapy should be employed, parents need to be informed when to discontinue therapy and that further research into the pharmacokinetics and pharmacogenetics of beta-blockers are warranted.”

Following publication of the case report in Pediatrics, Dr. Pope said that the only change she made in her practice was to ask families to temporarily discontinue nadolol if their child had constipation for more than 5 days.

The study was supported by a grant from Physician Services, Inc. Dr. Pope reported having no financial disclosures.

[email protected]

To the Editor:

Annular leukoderma, or the halo phenomenon, is a circular reaction of hypopigmentation that most commonly is observed alongside congenital nevi, acquired melanocytic nevi, blue nevi, Spitz nevi, vitiligo, and rarely melanoma.¹ There is limited literature on the mechanism of the halo phenomenon. Most of the literature proposes a T cell–mediated immune response to antigens, which causes not only surrounding pigment loss but also heralds the regression of central lesions.² Others have suggested a vascular mechanism, with blood shunted away from the lesions.³ Because guidelines discourage biopsy of typical halo nevi, it becomes important to evaluate lesions for worrisome features such as ulceration or asymmetry, especially in older patients. We present a case of a pigmented basal cell carcinoma (BCC) that exhibited the halo phenomenon. Four other cases have been described in the literature.^3-6

A 53-year-old man presented for evaluation of an asymptomatic lesion on the left side of the abdomen of approximately 8 months’ duration. He had no personal or family history of skin cancer. Physical examination revealed a central 1-cm, pink, verrucous papule surrounded by a 2×1.2-cm, depigmented, circular patch on the left side of the inferior abdomen (Figure 1). Upon questioning, the patient produced cell phone photographs of the trunk from 3 years prior, which did not show any lesions present. Full-body skin examination did not reveal any other concerning pigmented lesions. Excisional biopsy was performed due to concern for amelanotic melanoma, and histopathology revealed a superficial and pigmented BCC (Figure 2). Immunohistochemistry with Melan-A was negative for atypical melanocytes, with no uptake in the leukoderma areas.

Our patient’s final histologic diagnosis was pigmented BCC, which comprises only 6% of all BCCs.³ The proposed mechanism is that melanocytes colonize the tumor in the surrounding stroma and produce excess melanin. Basal cell carcinoma with halo phenomenon is a rare presentation. As in our case, 2 prior BCC reports also involved patients older than 50 years,^3,5 with the 2 other cases describing women in their late twenties and early thirties.^4,6 Additionally, 2 of 4 reports described patients with a history of multiple BCCs.^3,5

In summary, the seemingly benign halo phenomenon may accompany malignant processes such as nonmelanoma skin cancer. Careful consideration of lesion time course and atypia is imperative for proper clinical suspicion in such cases.

To the Editor:

Annular leukoderma, or the halo phenomenon, is a circular reaction of hypopigmentation that most commonly is observed alongside congenital nevi, acquired melanocytic nevi, blue nevi, Spitz nevi, vitiligo, and rarely melanoma.¹ There is limited literature on the mechanism of the halo phenomenon. Most of the literature proposes a T cell–mediated immune response to antigens, which causes not only surrounding pigment loss but also heralds the regression of central lesions.² Others have suggested a vascular mechanism, with blood shunted away from the lesions.³ Because guidelines discourage biopsy of typical halo nevi, it becomes important to evaluate lesions for worrisome features such as ulceration or asymmetry, especially in older patients. We present a case of a pigmented basal cell carcinoma (BCC) that exhibited the halo phenomenon. Four other cases have been described in the literature.^3-6

A 53-year-old man presented for evaluation of an asymptomatic lesion on the left side of the abdomen of approximately 8 months’ duration. He had no personal or family history of skin cancer. Physical examination revealed a central 1-cm, pink, verrucous papule surrounded by a 2×1.2-cm, depigmented, circular patch on the left side of the inferior abdomen (Figure 1). Upon questioning, the patient produced cell phone photographs of the trunk from 3 years prior, which did not show any lesions present. Full-body skin examination did not reveal any other concerning pigmented lesions. Excisional biopsy was performed due to concern for amelanotic melanoma, and histopathology revealed a superficial and pigmented BCC (Figure 2). Immunohistochemistry with Melan-A was negative for atypical melanocytes, with no uptake in the leukoderma areas.

Our patient’s final histologic diagnosis was pigmented BCC, which comprises only 6% of all BCCs.³ The proposed mechanism is that melanocytes colonize the tumor in the surrounding stroma and produce excess melanin. Basal cell carcinoma with halo phenomenon is a rare presentation. As in our case, 2 prior BCC reports also involved patients older than 50 years,^3,5 with the 2 other cases describing women in their late twenties and early thirties.^4,6 Additionally, 2 of 4 reports described patients with a history of multiple BCCs.^3,5

In summary, the seemingly benign halo phenomenon may accompany malignant processes such as nonmelanoma skin cancer. Careful consideration of lesion time course and atypia is imperative for proper clinical suspicion in such cases.

To the Editor:

Annular leukoderma, or the halo phenomenon, is a circular reaction of hypopigmentation that most commonly is observed alongside congenital nevi, acquired melanocytic nevi, blue nevi, Spitz nevi, vitiligo, and rarely melanoma.¹ There is limited literature on the mechanism of the halo phenomenon. Most of the literature proposes a T cell–mediated immune response to antigens, which causes not only surrounding pigment loss but also heralds the regression of central lesions.² Others have suggested a vascular mechanism, with blood shunted away from the lesions.³ Because guidelines discourage biopsy of typical halo nevi, it becomes important to evaluate lesions for worrisome features such as ulceration or asymmetry, especially in older patients. We present a case of a pigmented basal cell carcinoma (BCC) that exhibited the halo phenomenon. Four other cases have been described in the literature.^3-6

A 53-year-old man presented for evaluation of an asymptomatic lesion on the left side of the abdomen of approximately 8 months’ duration. He had no personal or family history of skin cancer. Physical examination revealed a central 1-cm, pink, verrucous papule surrounded by a 2×1.2-cm, depigmented, circular patch on the left side of the inferior abdomen (Figure 1). Upon questioning, the patient produced cell phone photographs of the trunk from 3 years prior, which did not show any lesions present. Full-body skin examination did not reveal any other concerning pigmented lesions. Excisional biopsy was performed due to concern for amelanotic melanoma, and histopathology revealed a superficial and pigmented BCC (Figure 2). Immunohistochemistry with Melan-A was negative for atypical melanocytes, with no uptake in the leukoderma areas.

Our patient’s final histologic diagnosis was pigmented BCC, which comprises only 6% of all BCCs.³ The proposed mechanism is that melanocytes colonize the tumor in the surrounding stroma and produce excess melanin. Basal cell carcinoma with halo phenomenon is a rare presentation. As in our case, 2 prior BCC reports also involved patients older than 50 years,^3,5 with the 2 other cases describing women in their late twenties and early thirties.^4,6 Additionally, 2 of 4 reports described patients with a history of multiple BCCs.^3,5

In summary, the seemingly benign halo phenomenon may accompany malignant processes such as nonmelanoma skin cancer. Careful consideration of lesion time course and atypia is imperative for proper clinical suspicion in such cases.

To the Editor:

Phacomatosis pigmentokeratotica (PPK) is a rare epidermal nevus syndrome complicated by multiple extracutaneous anomalies, including skeletal defects and neurologic anomalies. Less common associations include lateral curvature of the spine and hyperhidrosis. We present a patient with PPK and unilateral Raynaud phenomenon in addition to a segmental distribution of melanocytic nevi, hyperhidrosis, and scoliosis.

A 9-year-old girl was born with a yellow-orange alopecic plaque on the right side of the scalp (Figure 1). There also were 2 large, irregularly pigmented patches localized on the right side of the upper back and buttock. Over 3 years, numerous papular nevi developed within these pigmented patches and were diagnosed as speckled lentiginous nevi (Figure 2). In addition, numerous nevi of various sizes affected the right face, right shoulder, right arm (Figure 3), and right neck and were clearly demarcated along the midline. Several nevi also were noted within the nevus sebaceous on the right scalp. These skin lesions expanded progressively with age. At 6 years of age, she was diagnosed with hyperhidrosis of the right half of the body, which was most pronounced on the face. Raynaud phenomenon restricted to the right hand also was noted (Figure 4). Upon cold exposure, the digits become pale white, cold, and numb; then blue; and finally red. She lacked other features of connective tissue disease, and autoantibody testing was negative. She also was noted to have an abnormal lateral curvature of the spine (scoliosis). Auditory, ocular, and neurologic examinations were normal. Cranial and cerebral magnetic resonance imaging showed no central nervous system abnormalities. Her family history was negative for nevus spilus, nevus sebaceous, and neurofibromatosis. The clinical findings in our patient led to the diagnosis of PPK.

Raynaud phenomenon involving only the right hand was a unique finding in our patient. In 3 years of follow-up, our patient developed no evidence of connective tissue disease or other systemic illness. We speculate that Raynaud phenomenon of the right hand along with hyperhidrosis of the right side of the body could be a result of dysfunction of the autonomic nervous system. We propose that Raynaud phenomenon represents an unusual manifestation of PPK and may broaden the spectrum of extracutaneous anomalies associated with the disease. The finding of segmental nevi outside of the confines of the nevus spilus was another unusual manifestation of mosaicism.

To the Editor:

Phacomatosis pigmentokeratotica (PPK) is a rare epidermal nevus syndrome complicated by multiple extracutaneous anomalies, including skeletal defects and neurologic anomalies. Less common associations include lateral curvature of the spine and hyperhidrosis. We present a patient with PPK and unilateral Raynaud phenomenon in addition to a segmental distribution of melanocytic nevi, hyperhidrosis, and scoliosis.

A 9-year-old girl was born with a yellow-orange alopecic plaque on the right side of the scalp (Figure 1). There also were 2 large, irregularly pigmented patches localized on the right side of the upper back and buttock. Over 3 years, numerous papular nevi developed within these pigmented patches and were diagnosed as speckled lentiginous nevi (Figure 2). In addition, numerous nevi of various sizes affected the right face, right shoulder, right arm (Figure 3), and right neck and were clearly demarcated along the midline. Several nevi also were noted within the nevus sebaceous on the right scalp. These skin lesions expanded progressively with age. At 6 years of age, she was diagnosed with hyperhidrosis of the right half of the body, which was most pronounced on the face. Raynaud phenomenon restricted to the right hand also was noted (Figure 4). Upon cold exposure, the digits become pale white, cold, and numb; then blue; and finally red. She lacked other features of connective tissue disease, and autoantibody testing was negative. She also was noted to have an abnormal lateral curvature of the spine (scoliosis). Auditory, ocular, and neurologic examinations were normal. Cranial and cerebral magnetic resonance imaging showed no central nervous system abnormalities. Her family history was negative for nevus spilus, nevus sebaceous, and neurofibromatosis. The clinical findings in our patient led to the diagnosis of PPK.

Raynaud phenomenon involving only the right hand was a unique finding in our patient. In 3 years of follow-up, our patient developed no evidence of connective tissue disease or other systemic illness. We speculate that Raynaud phenomenon of the right hand along with hyperhidrosis of the right side of the body could be a result of dysfunction of the autonomic nervous system. We propose that Raynaud phenomenon represents an unusual manifestation of PPK and may broaden the spectrum of extracutaneous anomalies associated with the disease. The finding of segmental nevi outside of the confines of the nevus spilus was another unusual manifestation of mosaicism.

To the Editor:

Phacomatosis pigmentokeratotica (PPK) is a rare epidermal nevus syndrome complicated by multiple extracutaneous anomalies, including skeletal defects and neurologic anomalies. Less common associations include lateral curvature of the spine and hyperhidrosis. We present a patient with PPK and unilateral Raynaud phenomenon in addition to a segmental distribution of melanocytic nevi, hyperhidrosis, and scoliosis.

A 9-year-old girl was born with a yellow-orange alopecic plaque on the right side of the scalp (Figure 1). There also were 2 large, irregularly pigmented patches localized on the right side of the upper back and buttock. Over 3 years, numerous papular nevi developed within these pigmented patches and were diagnosed as speckled lentiginous nevi (Figure 2). In addition, numerous nevi of various sizes affected the right face, right shoulder, right arm (Figure 3), and right neck and were clearly demarcated along the midline. Several nevi also were noted within the nevus sebaceous on the right scalp. These skin lesions expanded progressively with age. At 6 years of age, she was diagnosed with hyperhidrosis of the right half of the body, which was most pronounced on the face. Raynaud phenomenon restricted to the right hand also was noted (Figure 4). Upon cold exposure, the digits become pale white, cold, and numb; then blue; and finally red. She lacked other features of connective tissue disease, and autoantibody testing was negative. She also was noted to have an abnormal lateral curvature of the spine (scoliosis). Auditory, ocular, and neurologic examinations were normal. Cranial and cerebral magnetic resonance imaging showed no central nervous system abnormalities. Her family history was negative for nevus spilus, nevus sebaceous, and neurofibromatosis. The clinical findings in our patient led to the diagnosis of PPK.

Raynaud phenomenon involving only the right hand was a unique finding in our patient. In 3 years of follow-up, our patient developed no evidence of connective tissue disease or other systemic illness. We speculate that Raynaud phenomenon of the right hand along with hyperhidrosis of the right side of the body could be a result of dysfunction of the autonomic nervous system. We propose that Raynaud phenomenon represents an unusual manifestation of PPK and may broaden the spectrum of extracutaneous anomalies associated with the disease. The finding of segmental nevi outside of the confines of the nevus spilus was another unusual manifestation of mosaicism.

The Diagnosis: Frontal Fibrosing Alopecia Overlapping With Lichen Planus Pigmentosus 

Microscopic examination revealed focal dermal pigmentation, papillary fibrosis, and epidermal atrophy. These clinical and histologic findings indicated a diagnosis of fully developed lichen planus pigmentosus (LPP) overlapping with frontal fibrosing alopecia (FFA). Other cases have demonstrated an association between LPP and FFA.^1,2  

Lichen planus pigmentosus is considered an uncommon variant of lichen planus, as it has similar histopathologic findings and occasional coexistence.^3,4 It is characterized by hyperpigmented macules primarily located in sun-exposed and flexural areas of the skin. First described in India,⁵ this disease has a predilection for darker skin (Fitzpatrick skin types III-V),^6,7 and it has been reported in other racial and ethnic groups including Latin Americans, Middle Eastern populations, Japanese, and Koreans.^4,8 Typically, lesions initially appear as ill-defined, blue-grey, round to oval macules that coalesce into hyperpigmented patches. Involvement most commonly begins at the forehead and temples, which are affected in nearly all patients. Infrequently, LPP can be generalized or affect the oral mucosa; involvement of the palms, soles, and nails does not occur. Patients may be asymptomatic, but some experience mild pruritus and burning. The disease course is chronic and insidious, with new lesions appearing over time and old lesions progressively darkening and expanding.^6,7,9  

Although the pathogenesis of LPP is unknown, several exposures have been implicated, such as amla oil, mustard oil, henna, hair dye, and environmental pollutants.⁷ Because lesions characteristically occur in sun-exposed areas, UV light also may be involved. In addition, studies have suggested that LPP is associated with endocrinopathies such as diabetes mellitus and dyslipidemias, as in our patient, as well as autoimmune conditions such as vitiligo and systemic lupus erythematosus.^10,11  

Histopathologic findings are characterized by vacuolar degeneration of the basal layer in the epidermis as well as perivascular lymphohistiocytic infiltration and the presence of melanophages in the dermis.^3,9 Lichen planus pigmentosus is difficult to treat, as no consistently effective modality has been established. Topical tacrolimus, topical corticosteroids, oral retinoids, lasers, and sun protection have been implemented with underwhelming results.¹² 

Frontal fibrosing alopecia is a variant of lichen planopilaris that predominantly affects postmenopausal women and presents with frontotemporal hair loss in a bandlike distribution.^5,13 Both terminal and vellus hairs are affected. Involvement of multiple hair-bearing sites of the skin have been reported, including the entire scalp, eyebrows, and eyelashes. Affected areas may display hypopigmentation and be accompanied by pruritus and trichodynia.^14,15 The pathogenesis currently is under investigation, with studies demonstrating autoimmune, genetic, and possibly even endocrine predispositions.^16-18 Biopsies of lesions are indistinguishable from lichen planopilaris, which shows follicular lymphocytic infiltration, perifollicular fibrosis, interface dermatitis of the follicular infundibulum and isthmus, and vertical fibrous tracks.⁵ Patients with FFA have demonstrated variable responses to treatments, with one study showing improvement with oral finasteride or dutasteride.¹⁴ Topical and intralesional corticosteroids have yielded suboptimal effects. Other modalities include hydroxychloroquine and mycophenolate mofetil.^15,19 

Co-occurrence of LPP and FFA primarily is seen in postmenopausal women with darker skin,^14,15 as in our patient, though premenopausal cases have been reported. Lichen planus pigmentosus may serve as a harbinger in most patients.^1,2 In a similar fashion, our patient presented with hyperpigmented macular lesions prior to the onset of frontotemporal hair loss.  

Our patient was started on finasteride 2.5 mg daily, minoxidil foam 5%, clobetasol solution 0.05%, triamcinolone ointment 0.1%, and hydrocortisone ointment 2.5%. She was instructed to commence treatment and follow up in 6 months. 

The differential diagnosis includes dermatologic conditions that mimic both LPP and FFA. Postinflammatory hyperpigmentation and fixed drug reaction were unlikely based on the patient's history. The lesions of ashy dermatosis are characteristically gray erythematous macules on the trunk and limbs. Riehl melanosis is a rare pigmented contact dermatitis that is associated with a history of repeated contact with sensitizing allergens. Although Hori nevus is characterized by small, blue-gray or brown macules on the face, lesions predominantly occur on the bony prominences of the cheeks. Melasma also presents with dark to gray macules that affect the face and less commonly the neck, as in our patient.² 

Early discoid lupus erythematosus presents with round erythematous plaques with overlying scale extending into the hair follicles. In pseudopalade of Brocq, an idiopathic cicatricial alopecia, lesions typically are flesh colored. Biopsy also shows epidermal atrophy with additional dermal sclerosis and fibrosis. Folliculitis decalvans is a scarring form of alopecia associated with erythema and pustules, findings that were not present in our patient. Keratosis follicularis spinulosa decalvans is a rare, X-linked inherited ichthyosis manifesting as scarring alopecia with follicular depressions and papules on the scalp in younger males. Photophobia and other manifestations may be present. Alopecia mucinosa is a nonscarring alopecia with grouped follicular erythematous patches or plaques. Mucin sometimes can be squeezed from affected areas, and histopathologic examination shows mucin accumulation.⁴ 

The Diagnosis: Frontal Fibrosing Alopecia Overlapping With Lichen Planus Pigmentosus 

Microscopic examination revealed focal dermal pigmentation, papillary fibrosis, and epidermal atrophy. These clinical and histologic findings indicated a diagnosis of fully developed lichen planus pigmentosus (LPP) overlapping with frontal fibrosing alopecia (FFA). Other cases have demonstrated an association between LPP and FFA.^1,2  

Lichen planus pigmentosus is considered an uncommon variant of lichen planus, as it has similar histopathologic findings and occasional coexistence.^3,4 It is characterized by hyperpigmented macules primarily located in sun-exposed and flexural areas of the skin. First described in India,⁵ this disease has a predilection for darker skin (Fitzpatrick skin types III-V),^6,7 and it has been reported in other racial and ethnic groups including Latin Americans, Middle Eastern populations, Japanese, and Koreans.^4,8 Typically, lesions initially appear as ill-defined, blue-grey, round to oval macules that coalesce into hyperpigmented patches. Involvement most commonly begins at the forehead and temples, which are affected in nearly all patients. Infrequently, LPP can be generalized or affect the oral mucosa; involvement of the palms, soles, and nails does not occur. Patients may be asymptomatic, but some experience mild pruritus and burning. The disease course is chronic and insidious, with new lesions appearing over time and old lesions progressively darkening and expanding.^6,7,9  

Although the pathogenesis of LPP is unknown, several exposures have been implicated, such as amla oil, mustard oil, henna, hair dye, and environmental pollutants.⁷ Because lesions characteristically occur in sun-exposed areas, UV light also may be involved. In addition, studies have suggested that LPP is associated with endocrinopathies such as diabetes mellitus and dyslipidemias, as in our patient, as well as autoimmune conditions such as vitiligo and systemic lupus erythematosus.^10,11  

Histopathologic findings are characterized by vacuolar degeneration of the basal layer in the epidermis as well as perivascular lymphohistiocytic infiltration and the presence of melanophages in the dermis.^3,9 Lichen planus pigmentosus is difficult to treat, as no consistently effective modality has been established. Topical tacrolimus, topical corticosteroids, oral retinoids, lasers, and sun protection have been implemented with underwhelming results.¹² 

Frontal fibrosing alopecia is a variant of lichen planopilaris that predominantly affects postmenopausal women and presents with frontotemporal hair loss in a bandlike distribution.^5,13 Both terminal and vellus hairs are affected. Involvement of multiple hair-bearing sites of the skin have been reported, including the entire scalp, eyebrows, and eyelashes. Affected areas may display hypopigmentation and be accompanied by pruritus and trichodynia.^14,15 The pathogenesis currently is under investigation, with studies demonstrating autoimmune, genetic, and possibly even endocrine predispositions.^16-18 Biopsies of lesions are indistinguishable from lichen planopilaris, which shows follicular lymphocytic infiltration, perifollicular fibrosis, interface dermatitis of the follicular infundibulum and isthmus, and vertical fibrous tracks.⁵ Patients with FFA have demonstrated variable responses to treatments, with one study showing improvement with oral finasteride or dutasteride.¹⁴ Topical and intralesional corticosteroids have yielded suboptimal effects. Other modalities include hydroxychloroquine and mycophenolate mofetil.^15,19 

Co-occurrence of LPP and FFA primarily is seen in postmenopausal women with darker skin,^14,15 as in our patient, though premenopausal cases have been reported. Lichen planus pigmentosus may serve as a harbinger in most patients.^1,2 In a similar fashion, our patient presented with hyperpigmented macular lesions prior to the onset of frontotemporal hair loss.  

Our patient was started on finasteride 2.5 mg daily, minoxidil foam 5%, clobetasol solution 0.05%, triamcinolone ointment 0.1%, and hydrocortisone ointment 2.5%. She was instructed to commence treatment and follow up in 6 months. 

The differential diagnosis includes dermatologic conditions that mimic both LPP and FFA. Postinflammatory hyperpigmentation and fixed drug reaction were unlikely based on the patient's history. The lesions of ashy dermatosis are characteristically gray erythematous macules on the trunk and limbs. Riehl melanosis is a rare pigmented contact dermatitis that is associated with a history of repeated contact with sensitizing allergens. Although Hori nevus is characterized by small, blue-gray or brown macules on the face, lesions predominantly occur on the bony prominences of the cheeks. Melasma also presents with dark to gray macules that affect the face and less commonly the neck, as in our patient.² 

Early discoid lupus erythematosus presents with round erythematous plaques with overlying scale extending into the hair follicles. In pseudopalade of Brocq, an idiopathic cicatricial alopecia, lesions typically are flesh colored. Biopsy also shows epidermal atrophy with additional dermal sclerosis and fibrosis. Folliculitis decalvans is a scarring form of alopecia associated with erythema and pustules, findings that were not present in our patient. Keratosis follicularis spinulosa decalvans is a rare, X-linked inherited ichthyosis manifesting as scarring alopecia with follicular depressions and papules on the scalp in younger males. Photophobia and other manifestations may be present. Alopecia mucinosa is a nonscarring alopecia with grouped follicular erythematous patches or plaques. Mucin sometimes can be squeezed from affected areas, and histopathologic examination shows mucin accumulation.⁴ 

The Diagnosis: Frontal Fibrosing Alopecia Overlapping With Lichen Planus Pigmentosus 

Microscopic examination revealed focal dermal pigmentation, papillary fibrosis, and epidermal atrophy. These clinical and histologic findings indicated a diagnosis of fully developed lichen planus pigmentosus (LPP) overlapping with frontal fibrosing alopecia (FFA). Other cases have demonstrated an association between LPP and FFA.^1,2  

Lichen planus pigmentosus is considered an uncommon variant of lichen planus, as it has similar histopathologic findings and occasional coexistence.^3,4 It is characterized by hyperpigmented macules primarily located in sun-exposed and flexural areas of the skin. First described in India,⁵ this disease has a predilection for darker skin (Fitzpatrick skin types III-V),^6,7 and it has been reported in other racial and ethnic groups including Latin Americans, Middle Eastern populations, Japanese, and Koreans.^4,8 Typically, lesions initially appear as ill-defined, blue-grey, round to oval macules that coalesce into hyperpigmented patches. Involvement most commonly begins at the forehead and temples, which are affected in nearly all patients. Infrequently, LPP can be generalized or affect the oral mucosa; involvement of the palms, soles, and nails does not occur. Patients may be asymptomatic, but some experience mild pruritus and burning. The disease course is chronic and insidious, with new lesions appearing over time and old lesions progressively darkening and expanding.^6,7,9  

Although the pathogenesis of LPP is unknown, several exposures have been implicated, such as amla oil, mustard oil, henna, hair dye, and environmental pollutants.⁷ Because lesions characteristically occur in sun-exposed areas, UV light also may be involved. In addition, studies have suggested that LPP is associated with endocrinopathies such as diabetes mellitus and dyslipidemias, as in our patient, as well as autoimmune conditions such as vitiligo and systemic lupus erythematosus.^10,11  

Histopathologic findings are characterized by vacuolar degeneration of the basal layer in the epidermis as well as perivascular lymphohistiocytic infiltration and the presence of melanophages in the dermis.^3,9 Lichen planus pigmentosus is difficult to treat, as no consistently effective modality has been established. Topical tacrolimus, topical corticosteroids, oral retinoids, lasers, and sun protection have been implemented with underwhelming results.¹² 

Frontal fibrosing alopecia is a variant of lichen planopilaris that predominantly affects postmenopausal women and presents with frontotemporal hair loss in a bandlike distribution.^5,13 Both terminal and vellus hairs are affected. Involvement of multiple hair-bearing sites of the skin have been reported, including the entire scalp, eyebrows, and eyelashes. Affected areas may display hypopigmentation and be accompanied by pruritus and trichodynia.^14,15 The pathogenesis currently is under investigation, with studies demonstrating autoimmune, genetic, and possibly even endocrine predispositions.^16-18 Biopsies of lesions are indistinguishable from lichen planopilaris, which shows follicular lymphocytic infiltration, perifollicular fibrosis, interface dermatitis of the follicular infundibulum and isthmus, and vertical fibrous tracks.⁵ Patients with FFA have demonstrated variable responses to treatments, with one study showing improvement with oral finasteride or dutasteride.¹⁴ Topical and intralesional corticosteroids have yielded suboptimal effects. Other modalities include hydroxychloroquine and mycophenolate mofetil.^15,19 

Co-occurrence of LPP and FFA primarily is seen in postmenopausal women with darker skin,^14,15 as in our patient, though premenopausal cases have been reported. Lichen planus pigmentosus may serve as a harbinger in most patients.^1,2 In a similar fashion, our patient presented with hyperpigmented macular lesions prior to the onset of frontotemporal hair loss.  

Our patient was started on finasteride 2.5 mg daily, minoxidil foam 5%, clobetasol solution 0.05%, triamcinolone ointment 0.1%, and hydrocortisone ointment 2.5%. She was instructed to commence treatment and follow up in 6 months. 

The differential diagnosis includes dermatologic conditions that mimic both LPP and FFA. Postinflammatory hyperpigmentation and fixed drug reaction were unlikely based on the patient's history. The lesions of ashy dermatosis are characteristically gray erythematous macules on the trunk and limbs. Riehl melanosis is a rare pigmented contact dermatitis that is associated with a history of repeated contact with sensitizing allergens. Although Hori nevus is characterized by small, blue-gray or brown macules on the face, lesions predominantly occur on the bony prominences of the cheeks. Melasma also presents with dark to gray macules that affect the face and less commonly the neck, as in our patient.² 

Early discoid lupus erythematosus presents with round erythematous plaques with overlying scale extending into the hair follicles. In pseudopalade of Brocq, an idiopathic cicatricial alopecia, lesions typically are flesh colored. Biopsy also shows epidermal atrophy with additional dermal sclerosis and fibrosis. Folliculitis decalvans is a scarring form of alopecia associated with erythema and pustules, findings that were not present in our patient. Keratosis follicularis spinulosa decalvans is a rare, X-linked inherited ichthyosis manifesting as scarring alopecia with follicular depressions and papules on the scalp in younger males. Photophobia and other manifestations may be present. Alopecia mucinosa is a nonscarring alopecia with grouped follicular erythematous patches or plaques. Mucin sometimes can be squeezed from affected areas, and histopathologic examination shows mucin accumulation.⁴ 

Patients with vitiligo have faced significant impacts psychosocially and in many cases, profound losses of identity – and they’ve had only minimal success with treatment, according to participants who spoke at and provided input at a public meeting on patient-focused drug development for the disease.

FG Trade/E+

The virtual meeting, held in March, was part of the Food and Drug Administration’s Patient-Focused Drug Development (PFDD) initiative, which began in 2012 and aims to provide a systematic way for patients’ experiences, needs and priorities to be “captured and meaningfully incorporated” into drug development and evaluation.

Seemal Desai, MD, of the department of dermatology at the University of Texas, Dallas, who attended the meeting as an observer, said in a later interview that while “all skin diseases have a psychosocial component … vitiligo is a really unique one, because it really relates to the patient’s own identity.

“What I heard loud and clear from the FDA [leaders who ran and attended the meeting] is recognition that patients are suffering. They needed to hear about the emotional devastation of the disease and how it is a medical condition,” Dr. Desai said.

The meeting was the “first-ever vitiligo meeting at the FDA” and was a “historic moment for the vitiligo community,” he added.

The pigmentation disorder affects 1% of the world’s population. Nearly 50% have an onset before age 20, and onset before age 12 is common, Brenda Carr, MD, medical officer with the FDA’s Division of Dermatology and Dentistry in the Center for Drug Evaluation and Research, said in an introductory overview.

The only FDA-approved treatment for vitiligo is monobenzone cream, but this is indicated for final depigmentation in extensive vitiligo and is no longer marketed. Treatment options include corticosteroids, calcineurin inhibitors, vitamin D analogues, phototherapy, surgical treatments (tissue grafts and cellular grafts), and camouflage (make-up, tattoos, self-tanning products), Dr. Carr said.

Patients participated in one of two panels – one about the health effects and daily impacts of vitiligo and the other about treatments – or submitted input electronically. All patients were invited to answer poll questions and open-ended queries, including questions about how they would assess new treatments.

Several panel members who are Black shared series of photos that showed the evolution of defined white patches into widespread, generalized depigmentation. One man with skin of color who lives in the Netherlands said he has had vitiligo since the age of 12, but that when he became older, over a 4-year period, he was “transformed from a man of Indonesian roots to a totally white man.”

Experiencing only minimal benefit from treatment and the short-term effectiveness of treatments were the top two answers to a poll question asking participants about the most burdensome impacts of the medical products and interventions they have used. Difficulty in accessing treatment, concern about serious risks of treatment, and uncertainty about long-term effects of treatment were other frequently chosen answers.

Patients described the onerous nature of phototherapy (treatments repeated several times a week over long periods) and other treatments, and several described feeling that some physicians did not take the condition seriously or fully know of treatment options.

In her closing remarks, Kendall Marcus, MD, director of the Division of Dermatology and Dentistry at the FDA, acknowledged the input. “Some of you have had difficulty having your disease taken seriously by physicians who view it as a cosmetic condition and are reluctant to treat because they believe your expectations will not be met, that it will be an exercise in frustration,” she said.

Regarding the impacts of treatments that have been utilized, “some of the treatments make it impossible to do other activities such as work or care for yourself in other ways,” Dr. Marcus said. “Certainly that’s not the kind of treatment … that anybody wants to have.”

Dr. Desai, who utilizes an array of oral and topical treatments and phototherapies in his practice, said he was surprised and disheartened to hear the level of concern about side effects of treatment. Most of those who expressed concerns alluded to phototherapy. “I think light treatments are very safe and effective,” he said in the interview. “I might equate [such concerns] to the older PUVA [psoralen plus UVA ultraviolet light] therapy, but not so much the newer therapies.”

The FDA participants probed patients for their perspective on a meaningful level of repigmentation and an acceptable level of risk for any new hypothetical treatment. Specifically, they asked whether patients would use a new topical cream approved for vitiligo if the cream needed to be applied once a day, would have up to 50% efficacy in some people, and would have common side effects of redness and irritation at the application site, mild acne, and burning, as well as several rarer but more serious side effects.

Only 36% answered yes; 24% said no, and 40% answered maybe. Some patients said during the meeting that they had accepted their condition and were not pursuing any treatment. Others said they were very interested in treatment but only if the level of repigmentation were significantly higher than 50%. Some described their fear that positive treatment effects would be short term only.

Meri Izrail Kohen, who lives in France and has lost half of her skin’s pigmentation, said that treatment efficacy is “not only about how much recovery of pigment it allows, but how long the recovery will last.” Some treatments will work for some patients, she said, “but even in these cases when we stop the treatment, it will come back somehow.”

Lee Thomas, a TV anchor in Detroit, and a reporter and author of the book “Turning White,” described how he tried “every treatment he could afford” but stopped trying 10 years ago. A treatment in Germany “gave me 80% of my pigment back, but it has gone again,” he said. “I would love to have my face back again. I was born a Black child, and I’d like to die a Black man.”

Patients also spoke of their skin burning easily outdoors; skin sensitivity, itchiness, and burning with the spread of disease; treatment expenses and not being able to afford treatment; and worsening of their vitiligo with the stress of the pandemic. Parents expressed having fear that their children would develop vitiligo and experience bullying, isolation, or other emotional or psychosocial impacts that they had experienced; one described having an almost-paralyzing anxiety when he saw patchy white spots on his 20-month-old daughter (it was not diagnosed as vitiligo).

Calls for further advancement with home phototherapy – which Dr. Desai said is a growing market but not yet adequately covered by insurance plans – were also made, as were pleas for research on the root causes of the disease.

Patients clearly indicated “that they need more efficacious treatments, and more comprehensive treatments,” said Dr. Desai, who chairs the advisory committee of the Global Vitiligo Foundation. “It’s disappointing to me that patients come in with a not fully optimistic viewpoint, with a lot of anxiety and angst that treatments are not going to work. … But the Agency needs to hear that. This means that there haven’t been good treatments and we need more.”

The FDA will accept public comments until May 10, 2021, at which time comments will be compiled into a summary report. FDA officials assured patients that the report would be visible and circulated not only within the FDA but among drug companies, researchers, and other product developers.

Patients with vitiligo have faced significant impacts psychosocially and in many cases, profound losses of identity – and they’ve had only minimal success with treatment, according to participants who spoke at and provided input at a public meeting on patient-focused drug development for the disease.

FG Trade/E+

The virtual meeting, held in March, was part of the Food and Drug Administration’s Patient-Focused Drug Development (PFDD) initiative, which began in 2012 and aims to provide a systematic way for patients’ experiences, needs and priorities to be “captured and meaningfully incorporated” into drug development and evaluation.

Seemal Desai, MD, of the department of dermatology at the University of Texas, Dallas, who attended the meeting as an observer, said in a later interview that while “all skin diseases have a psychosocial component … vitiligo is a really unique one, because it really relates to the patient’s own identity.

“What I heard loud and clear from the FDA [leaders who ran and attended the meeting] is recognition that patients are suffering. They needed to hear about the emotional devastation of the disease and how it is a medical condition,” Dr. Desai said.

The meeting was the “first-ever vitiligo meeting at the FDA” and was a “historic moment for the vitiligo community,” he added.

The pigmentation disorder affects 1% of the world’s population. Nearly 50% have an onset before age 20, and onset before age 12 is common, Brenda Carr, MD, medical officer with the FDA’s Division of Dermatology and Dentistry in the Center for Drug Evaluation and Research, said in an introductory overview.

The only FDA-approved treatment for vitiligo is monobenzone cream, but this is indicated for final depigmentation in extensive vitiligo and is no longer marketed. Treatment options include corticosteroids, calcineurin inhibitors, vitamin D analogues, phototherapy, surgical treatments (tissue grafts and cellular grafts), and camouflage (make-up, tattoos, self-tanning products), Dr. Carr said.

Patients participated in one of two panels – one about the health effects and daily impacts of vitiligo and the other about treatments – or submitted input electronically. All patients were invited to answer poll questions and open-ended queries, including questions about how they would assess new treatments.

Several panel members who are Black shared series of photos that showed the evolution of defined white patches into widespread, generalized depigmentation. One man with skin of color who lives in the Netherlands said he has had vitiligo since the age of 12, but that when he became older, over a 4-year period, he was “transformed from a man of Indonesian roots to a totally white man.”

Experiencing only minimal benefit from treatment and the short-term effectiveness of treatments were the top two answers to a poll question asking participants about the most burdensome impacts of the medical products and interventions they have used. Difficulty in accessing treatment, concern about serious risks of treatment, and uncertainty about long-term effects of treatment were other frequently chosen answers.

Patients described the onerous nature of phototherapy (treatments repeated several times a week over long periods) and other treatments, and several described feeling that some physicians did not take the condition seriously or fully know of treatment options.

In her closing remarks, Kendall Marcus, MD, director of the Division of Dermatology and Dentistry at the FDA, acknowledged the input. “Some of you have had difficulty having your disease taken seriously by physicians who view it as a cosmetic condition and are reluctant to treat because they believe your expectations will not be met, that it will be an exercise in frustration,” she said.

Regarding the impacts of treatments that have been utilized, “some of the treatments make it impossible to do other activities such as work or care for yourself in other ways,” Dr. Marcus said. “Certainly that’s not the kind of treatment … that anybody wants to have.”

Dr. Desai, who utilizes an array of oral and topical treatments and phototherapies in his practice, said he was surprised and disheartened to hear the level of concern about side effects of treatment. Most of those who expressed concerns alluded to phototherapy. “I think light treatments are very safe and effective,” he said in the interview. “I might equate [such concerns] to the older PUVA [psoralen plus UVA ultraviolet light] therapy, but not so much the newer therapies.”

The FDA participants probed patients for their perspective on a meaningful level of repigmentation and an acceptable level of risk for any new hypothetical treatment. Specifically, they asked whether patients would use a new topical cream approved for vitiligo if the cream needed to be applied once a day, would have up to 50% efficacy in some people, and would have common side effects of redness and irritation at the application site, mild acne, and burning, as well as several rarer but more serious side effects.

Only 36% answered yes; 24% said no, and 40% answered maybe. Some patients said during the meeting that they had accepted their condition and were not pursuing any treatment. Others said they were very interested in treatment but only if the level of repigmentation were significantly higher than 50%. Some described their fear that positive treatment effects would be short term only.

Meri Izrail Kohen, who lives in France and has lost half of her skin’s pigmentation, said that treatment efficacy is “not only about how much recovery of pigment it allows, but how long the recovery will last.” Some treatments will work for some patients, she said, “but even in these cases when we stop the treatment, it will come back somehow.”

Lee Thomas, a TV anchor in Detroit, and a reporter and author of the book “Turning White,” described how he tried “every treatment he could afford” but stopped trying 10 years ago. A treatment in Germany “gave me 80% of my pigment back, but it has gone again,” he said. “I would love to have my face back again. I was born a Black child, and I’d like to die a Black man.”

Patients also spoke of their skin burning easily outdoors; skin sensitivity, itchiness, and burning with the spread of disease; treatment expenses and not being able to afford treatment; and worsening of their vitiligo with the stress of the pandemic. Parents expressed having fear that their children would develop vitiligo and experience bullying, isolation, or other emotional or psychosocial impacts that they had experienced; one described having an almost-paralyzing anxiety when he saw patchy white spots on his 20-month-old daughter (it was not diagnosed as vitiligo).

Calls for further advancement with home phototherapy – which Dr. Desai said is a growing market but not yet adequately covered by insurance plans – were also made, as were pleas for research on the root causes of the disease.

Patients clearly indicated “that they need more efficacious treatments, and more comprehensive treatments,” said Dr. Desai, who chairs the advisory committee of the Global Vitiligo Foundation. “It’s disappointing to me that patients come in with a not fully optimistic viewpoint, with a lot of anxiety and angst that treatments are not going to work. … But the Agency needs to hear that. This means that there haven’t been good treatments and we need more.”

The FDA will accept public comments until May 10, 2021, at which time comments will be compiled into a summary report. FDA officials assured patients that the report would be visible and circulated not only within the FDA but among drug companies, researchers, and other product developers.

Patients with vitiligo have faced significant impacts psychosocially and in many cases, profound losses of identity – and they’ve had only minimal success with treatment, according to participants who spoke at and provided input at a public meeting on patient-focused drug development for the disease.

FG Trade/E+

The virtual meeting, held in March, was part of the Food and Drug Administration’s Patient-Focused Drug Development (PFDD) initiative, which began in 2012 and aims to provide a systematic way for patients’ experiences, needs and priorities to be “captured and meaningfully incorporated” into drug development and evaluation.

Seemal Desai, MD, of the department of dermatology at the University of Texas, Dallas, who attended the meeting as an observer, said in a later interview that while “all skin diseases have a psychosocial component … vitiligo is a really unique one, because it really relates to the patient’s own identity.

“What I heard loud and clear from the FDA [leaders who ran and attended the meeting] is recognition that patients are suffering. They needed to hear about the emotional devastation of the disease and how it is a medical condition,” Dr. Desai said.

The meeting was the “first-ever vitiligo meeting at the FDA” and was a “historic moment for the vitiligo community,” he added.

The pigmentation disorder affects 1% of the world’s population. Nearly 50% have an onset before age 20, and onset before age 12 is common, Brenda Carr, MD, medical officer with the FDA’s Division of Dermatology and Dentistry in the Center for Drug Evaluation and Research, said in an introductory overview.

The only FDA-approved treatment for vitiligo is monobenzone cream, but this is indicated for final depigmentation in extensive vitiligo and is no longer marketed. Treatment options include corticosteroids, calcineurin inhibitors, vitamin D analogues, phototherapy, surgical treatments (tissue grafts and cellular grafts), and camouflage (make-up, tattoos, self-tanning products), Dr. Carr said.

Patients participated in one of two panels – one about the health effects and daily impacts of vitiligo and the other about treatments – or submitted input electronically. All patients were invited to answer poll questions and open-ended queries, including questions about how they would assess new treatments.

Several panel members who are Black shared series of photos that showed the evolution of defined white patches into widespread, generalized depigmentation. One man with skin of color who lives in the Netherlands said he has had vitiligo since the age of 12, but that when he became older, over a 4-year period, he was “transformed from a man of Indonesian roots to a totally white man.”

Experiencing only minimal benefit from treatment and the short-term effectiveness of treatments were the top two answers to a poll question asking participants about the most burdensome impacts of the medical products and interventions they have used. Difficulty in accessing treatment, concern about serious risks of treatment, and uncertainty about long-term effects of treatment were other frequently chosen answers.

Patients described the onerous nature of phototherapy (treatments repeated several times a week over long periods) and other treatments, and several described feeling that some physicians did not take the condition seriously or fully know of treatment options.

In her closing remarks, Kendall Marcus, MD, director of the Division of Dermatology and Dentistry at the FDA, acknowledged the input. “Some of you have had difficulty having your disease taken seriously by physicians who view it as a cosmetic condition and are reluctant to treat because they believe your expectations will not be met, that it will be an exercise in frustration,” she said.

Regarding the impacts of treatments that have been utilized, “some of the treatments make it impossible to do other activities such as work or care for yourself in other ways,” Dr. Marcus said. “Certainly that’s not the kind of treatment … that anybody wants to have.”

Dr. Desai, who utilizes an array of oral and topical treatments and phototherapies in his practice, said he was surprised and disheartened to hear the level of concern about side effects of treatment. Most of those who expressed concerns alluded to phototherapy. “I think light treatments are very safe and effective,” he said in the interview. “I might equate [such concerns] to the older PUVA [psoralen plus UVA ultraviolet light] therapy, but not so much the newer therapies.”

The FDA participants probed patients for their perspective on a meaningful level of repigmentation and an acceptable level of risk for any new hypothetical treatment. Specifically, they asked whether patients would use a new topical cream approved for vitiligo if the cream needed to be applied once a day, would have up to 50% efficacy in some people, and would have common side effects of redness and irritation at the application site, mild acne, and burning, as well as several rarer but more serious side effects.

Only 36% answered yes; 24% said no, and 40% answered maybe. Some patients said during the meeting that they had accepted their condition and were not pursuing any treatment. Others said they were very interested in treatment but only if the level of repigmentation were significantly higher than 50%. Some described their fear that positive treatment effects would be short term only.

Meri Izrail Kohen, who lives in France and has lost half of her skin’s pigmentation, said that treatment efficacy is “not only about how much recovery of pigment it allows, but how long the recovery will last.” Some treatments will work for some patients, she said, “but even in these cases when we stop the treatment, it will come back somehow.”

Lee Thomas, a TV anchor in Detroit, and a reporter and author of the book “Turning White,” described how he tried “every treatment he could afford” but stopped trying 10 years ago. A treatment in Germany “gave me 80% of my pigment back, but it has gone again,” he said. “I would love to have my face back again. I was born a Black child, and I’d like to die a Black man.”

Patients also spoke of their skin burning easily outdoors; skin sensitivity, itchiness, and burning with the spread of disease; treatment expenses and not being able to afford treatment; and worsening of their vitiligo with the stress of the pandemic. Parents expressed having fear that their children would develop vitiligo and experience bullying, isolation, or other emotional or psychosocial impacts that they had experienced; one described having an almost-paralyzing anxiety when he saw patchy white spots on his 20-month-old daughter (it was not diagnosed as vitiligo).

Calls for further advancement with home phototherapy – which Dr. Desai said is a growing market but not yet adequately covered by insurance plans – were also made, as were pleas for research on the root causes of the disease.

Patients clearly indicated “that they need more efficacious treatments, and more comprehensive treatments,” said Dr. Desai, who chairs the advisory committee of the Global Vitiligo Foundation. “It’s disappointing to me that patients come in with a not fully optimistic viewpoint, with a lot of anxiety and angst that treatments are not going to work. … But the Agency needs to hear that. This means that there haven’t been good treatments and we need more.”

The FDA will accept public comments until May 10, 2021, at which time comments will be compiled into a summary report. FDA officials assured patients that the report would be visible and circulated not only within the FDA but among drug companies, researchers, and other product developers.

The first rule about infantile hemangiomas: Make sure they’re actually infantile hemangiomas, a pediatric dermatologist urged colleagues. Then watch patients closely, refer to specialists when appropriate, and consider propranolol in complicated or high-risk cases, Andrea L. Zaenglein, MD, said at MedscapeLive’s Women’s & Pediatric Dermatology Seminar.

“In my career as a pediatric dermatologist, propranolol has been a life changer for us more than any other medicine,” said Dr. Zaenglein, professor of dermatology and pediatric dermatology, Penn State University, Hershey.

Before the point where propranolol is prescribed, confirm the diagnosis and use the correct terminology, she advised. It’s still appropriate to use the International Society for the Study of Vascular Anomalies (ISSVA) vascular lesion classification system released in 1982. “For most people, it serves the purpose well,” she said. Another option is an updated and more complex classification system from 2015.

Dr. Zaenglein highlighted two studies – one published in 2011 and the other published in 2020 – that revealed high levels of misclassification of vascular malformations in research reports. The earlier study found that 21% of patients with misclassified lesions were mistreated, compared with none of those who were classified using ISSVA terminology.

“I cannot stress [proper classification] enough when you’re dealing with babies and children with vascular lesions. If not sure, be vague. Say ‘a vascular tumor’ or a ‘vascular malformation.’ But only reserve ‘infantile hemangioma’ for that very diagnosis,” she said.

As Dr. Zaenglein noted, infantile hemangiomas affect 5%-10% of 1-year-olds, of whom 20% have multiple lesions. They’re more common in females by a 3-to-1 margin, and also seen more in premature infants, and in cases of multiple births, higher maternal age, and low birth weight.

The pathogenesis of these lesions is unclear, she said, although there are hints about genetic components and tissue hypoxia, among other possible causes. “Importantly, you get 80% of the growth by 3-4 months of age. Then it’ll slow in its growth and kind of slowly go away over time, but it’s not linear regression. It’s more that you get more improvement up front, usually until about 5, and then you can get some continued gradual evolution up until about 7 or 10 years of age.”

Complications can include ulceration, infection and – in rare cases – hemorrhage and high-output cardiac failure, she said. “Knowing which ones are at high risk for complications is important, and also there are systemic associations that we have to be mindful of. We also want to think about aesthetic outcomes as well when we talk about management of infantile hemangiomas.”

High-risk infantile hemangiomas include those with the following features:

• Extensive facial involvement. Dr. Zaenglein highlighted a case of a 2-year-old baby with a large, bulky hemangioma that distorted facial features around the eye. “This would be a medical emergency” requiring immediate evaluation and treatment, she said.
• Periocular involvement. Refer to ophthalmology, she recommended. “Even smaller hemangiomas can cause refractive errors or amblyopia, and oftentimes need to be treated with either systemic or topical therapy depending on the size and extent,” she said.
• PHACE syndrome (Posterior fossa malformations, hemangiomas, arterial anomalies, coarctation of the aorta and cardiac defects, eye abnormalities). “Propranolol has been safely used in PHACE, but every patient is different,” she said. “You need to make sure to do a good risk assessment before starting because if they have narrowed blood flow or limited blood flow, there is a question of whether there is potential risk for stroke if you drop a baby’s blood pressure. Make sure that the vasculature is evaluated before started on propranolol. Also, there are recent reports of risk of long-term risk of stroke with PHACE syndrome as patients are getting into their adulthood.”
• Beard distribution. Be aware of possible airway involvement that can be revealed by biphasic stridor. In those cases, immediate treatment – perhaps even with tracheostomy – is needed to avoid mortality, she said.
• Multiple sites: Patients with five or more hemangiomas may have liver involvement, she said, and should undergo hepatic evaluation. Consider evaluating if this is suspected, even if the number of hemangiomas is under five, she said.
• Perineal/lumbosacral involvement: A third of these cases are associated with spinal dysraphism. Refer to neurosurgery, she recommended.

Dr. Zaenglein highlighted a report on the use of propranolol published in 2008 and noted that clinical practice guidelines for managing infantile hemangiomas published in 2019 are also helpful.

Flat hemangiomas, meanwhile, can benefit from timolol maleate 0.5% solution or gel-forming solution – 1 drop twice daily or 2 drops once daily, she said. This treatment should be avoided in thick hemangiomas, she said.

MedscapeLive and this news organization are owned by the same parent company. Dr. Zaenglein disclosed consulting fees (Dermata, Cassiopea, and Regeneron), and fees for contracted research support (Incyte).

The first rule about infantile hemangiomas: Make sure they’re actually infantile hemangiomas, a pediatric dermatologist urged colleagues. Then watch patients closely, refer to specialists when appropriate, and consider propranolol in complicated or high-risk cases, Andrea L. Zaenglein, MD, said at MedscapeLive’s Women’s & Pediatric Dermatology Seminar.

“In my career as a pediatric dermatologist, propranolol has been a life changer for us more than any other medicine,” said Dr. Zaenglein, professor of dermatology and pediatric dermatology, Penn State University, Hershey.

Before the point where propranolol is prescribed, confirm the diagnosis and use the correct terminology, she advised. It’s still appropriate to use the International Society for the Study of Vascular Anomalies (ISSVA) vascular lesion classification system released in 1982. “For most people, it serves the purpose well,” she said. Another option is an updated and more complex classification system from 2015.

Dr. Zaenglein highlighted two studies – one published in 2011 and the other published in 2020 – that revealed high levels of misclassification of vascular malformations in research reports. The earlier study found that 21% of patients with misclassified lesions were mistreated, compared with none of those who were classified using ISSVA terminology.

“I cannot stress [proper classification] enough when you’re dealing with babies and children with vascular lesions. If not sure, be vague. Say ‘a vascular tumor’ or a ‘vascular malformation.’ But only reserve ‘infantile hemangioma’ for that very diagnosis,” she said.

As Dr. Zaenglein noted, infantile hemangiomas affect 5%-10% of 1-year-olds, of whom 20% have multiple lesions. They’re more common in females by a 3-to-1 margin, and also seen more in premature infants, and in cases of multiple births, higher maternal age, and low birth weight.

The pathogenesis of these lesions is unclear, she said, although there are hints about genetic components and tissue hypoxia, among other possible causes. “Importantly, you get 80% of the growth by 3-4 months of age. Then it’ll slow in its growth and kind of slowly go away over time, but it’s not linear regression. It’s more that you get more improvement up front, usually until about 5, and then you can get some continued gradual evolution up until about 7 or 10 years of age.”

Complications can include ulceration, infection and – in rare cases – hemorrhage and high-output cardiac failure, she said. “Knowing which ones are at high risk for complications is important, and also there are systemic associations that we have to be mindful of. We also want to think about aesthetic outcomes as well when we talk about management of infantile hemangiomas.”

High-risk infantile hemangiomas include those with the following features:

• Extensive facial involvement. Dr. Zaenglein highlighted a case of a 2-year-old baby with a large, bulky hemangioma that distorted facial features around the eye. “This would be a medical emergency” requiring immediate evaluation and treatment, she said.
• Periocular involvement. Refer to ophthalmology, she recommended. “Even smaller hemangiomas can cause refractive errors or amblyopia, and oftentimes need to be treated with either systemic or topical therapy depending on the size and extent,” she said.
• PHACE syndrome (Posterior fossa malformations, hemangiomas, arterial anomalies, coarctation of the aorta and cardiac defects, eye abnormalities). “Propranolol has been safely used in PHACE, but every patient is different,” she said. “You need to make sure to do a good risk assessment before starting because if they have narrowed blood flow or limited blood flow, there is a question of whether there is potential risk for stroke if you drop a baby’s blood pressure. Make sure that the vasculature is evaluated before started on propranolol. Also, there are recent reports of risk of long-term risk of stroke with PHACE syndrome as patients are getting into their adulthood.”
• Beard distribution. Be aware of possible airway involvement that can be revealed by biphasic stridor. In those cases, immediate treatment – perhaps even with tracheostomy – is needed to avoid mortality, she said.
• Multiple sites: Patients with five or more hemangiomas may have liver involvement, she said, and should undergo hepatic evaluation. Consider evaluating if this is suspected, even if the number of hemangiomas is under five, she said.
• Perineal/lumbosacral involvement: A third of these cases are associated with spinal dysraphism. Refer to neurosurgery, she recommended.

Dr. Zaenglein highlighted a report on the use of propranolol published in 2008 and noted that clinical practice guidelines for managing infantile hemangiomas published in 2019 are also helpful.

Flat hemangiomas, meanwhile, can benefit from timolol maleate 0.5% solution or gel-forming solution – 1 drop twice daily or 2 drops once daily, she said. This treatment should be avoided in thick hemangiomas, she said.

MedscapeLive and this news organization are owned by the same parent company. Dr. Zaenglein disclosed consulting fees (Dermata, Cassiopea, and Regeneron), and fees for contracted research support (Incyte).

The first rule about infantile hemangiomas: Make sure they’re actually infantile hemangiomas, a pediatric dermatologist urged colleagues. Then watch patients closely, refer to specialists when appropriate, and consider propranolol in complicated or high-risk cases, Andrea L. Zaenglein, MD, said at MedscapeLive’s Women’s & Pediatric Dermatology Seminar.

“In my career as a pediatric dermatologist, propranolol has been a life changer for us more than any other medicine,” said Dr. Zaenglein, professor of dermatology and pediatric dermatology, Penn State University, Hershey.

Before the point where propranolol is prescribed, confirm the diagnosis and use the correct terminology, she advised. It’s still appropriate to use the International Society for the Study of Vascular Anomalies (ISSVA) vascular lesion classification system released in 1982. “For most people, it serves the purpose well,” she said. Another option is an updated and more complex classification system from 2015.

Dr. Zaenglein highlighted two studies – one published in 2011 and the other published in 2020 – that revealed high levels of misclassification of vascular malformations in research reports. The earlier study found that 21% of patients with misclassified lesions were mistreated, compared with none of those who were classified using ISSVA terminology.

“I cannot stress [proper classification] enough when you’re dealing with babies and children with vascular lesions. If not sure, be vague. Say ‘a vascular tumor’ or a ‘vascular malformation.’ But only reserve ‘infantile hemangioma’ for that very diagnosis,” she said.

As Dr. Zaenglein noted, infantile hemangiomas affect 5%-10% of 1-year-olds, of whom 20% have multiple lesions. They’re more common in females by a 3-to-1 margin, and also seen more in premature infants, and in cases of multiple births, higher maternal age, and low birth weight.

The pathogenesis of these lesions is unclear, she said, although there are hints about genetic components and tissue hypoxia, among other possible causes. “Importantly, you get 80% of the growth by 3-4 months of age. Then it’ll slow in its growth and kind of slowly go away over time, but it’s not linear regression. It’s more that you get more improvement up front, usually until about 5, and then you can get some continued gradual evolution up until about 7 or 10 years of age.”

Complications can include ulceration, infection and – in rare cases – hemorrhage and high-output cardiac failure, she said. “Knowing which ones are at high risk for complications is important, and also there are systemic associations that we have to be mindful of. We also want to think about aesthetic outcomes as well when we talk about management of infantile hemangiomas.”

High-risk infantile hemangiomas include those with the following features:

• Extensive facial involvement. Dr. Zaenglein highlighted a case of a 2-year-old baby with a large, bulky hemangioma that distorted facial features around the eye. “This would be a medical emergency” requiring immediate evaluation and treatment, she said.
• Periocular involvement. Refer to ophthalmology, she recommended. “Even smaller hemangiomas can cause refractive errors or amblyopia, and oftentimes need to be treated with either systemic or topical therapy depending on the size and extent,” she said.
• PHACE syndrome (Posterior fossa malformations, hemangiomas, arterial anomalies, coarctation of the aorta and cardiac defects, eye abnormalities). “Propranolol has been safely used in PHACE, but every patient is different,” she said. “You need to make sure to do a good risk assessment before starting because if they have narrowed blood flow or limited blood flow, there is a question of whether there is potential risk for stroke if you drop a baby’s blood pressure. Make sure that the vasculature is evaluated before started on propranolol. Also, there are recent reports of risk of long-term risk of stroke with PHACE syndrome as patients are getting into their adulthood.”
• Beard distribution. Be aware of possible airway involvement that can be revealed by biphasic stridor. In those cases, immediate treatment – perhaps even with tracheostomy – is needed to avoid mortality, she said.
• Multiple sites: Patients with five or more hemangiomas may have liver involvement, she said, and should undergo hepatic evaluation. Consider evaluating if this is suspected, even if the number of hemangiomas is under five, she said.
• Perineal/lumbosacral involvement: A third of these cases are associated with spinal dysraphism. Refer to neurosurgery, she recommended.

Dr. Zaenglein highlighted a report on the use of propranolol published in 2008 and noted that clinical practice guidelines for managing infantile hemangiomas published in 2019 are also helpful.

Flat hemangiomas, meanwhile, can benefit from timolol maleate 0.5% solution or gel-forming solution – 1 drop twice daily or 2 drops once daily, she said. This treatment should be avoided in thick hemangiomas, she said.

MedscapeLive and this news organization are owned by the same parent company. Dr. Zaenglein disclosed consulting fees (Dermata, Cassiopea, and Regeneron), and fees for contracted research support (Incyte).