Hair & Nails

To the Editor:

Both alopecia areata (AA) and psoriasis vulgaris are chronic relapsing autoimmune diseases, with AA causing nonscarring hair loss in approximately 0.1% to 0.2%¹ of the population with a lifetime risk of 1.7%,² and psoriasis more broadly impacting 1.5% to 2% of the population.³ The helper T cell (T_H1) cytokine milieu is pathogenic in both conditions.^4-6 IFN-γ knockout mice, unlike their wild-type counterparts, do not exhibit AA.⁷ Psoriasis is notably improved by IL-10 injections, which dampen the T_H1 response.⁸ Distinct from AA, T_H17 and T_H22 cells have been implicated as key players in psoriasis pathogenesis, along with the associated IL-17 and IL-22 cytokines.^9-12

Few cases of patients with concurrent AA and psoriasis have been described. Interestingly, these cases document normal hair regrowth in the areas of psoriasis.^13-16 These cases may offer unique insight into the immune factors driving each disease. We describe a case of a man with both alopecia universalis (AU) and psoriasis who developed hair regrowth in some of the psoriatic plaques.

A 34-year-old man with concurrent AU and psoriasis who had not used any systemic or topical medication for either condition in the last year presented to our clinic seeking treatment. The patient had a history of alopecia totalis as a toddler that completely resolved by 4 years of age with the use of squaric acid dibutylester (SADBE). At 31 years of age, the alopecia recurred and was localized to the scalp. It was partially responsive to intralesional triamcinolone acetonide. The patient’s alopecia worsened over the 2 years following recurrence, ultimately progressing to AU. Two months after the alopecia recurrence, he developed the first psoriatic plaques. As the plaque psoriasis progressed, systemic therapy was initiated, first methotrexate and then etanercept. Shortly after developing AU, he lost his health insurance and discontinued all therapy. The patient’s psoriasis began to recur approximately 3 months after stopping etanercept. He was not using any other psoriasis medications. At that time, he noted terminal hair regrowth within some of the psoriatic plaques. No terminal hairs grew outside of the psoriatic plaques, and all regions with growth had previously been without hair for an extended period of time. The patient presented to our clinic approximately 1 year later. He had no other medical conditions and no relevant family history.

On initial physical examination, he had nonscarring hair loss involving nearly 100% of the body with psoriatic plaques on approximately 30% of the body surface area. Regions of terminal hair growth were confined to some but not all of the psoriatic plaques (Figure). Interestingly, the terminal hairs were primarily localized to the thickest central regions of the plaques. The patient’s psoriasis was treated with a combination of topical clobetasol and calcipotriene. In addition, he was started on tacrolimus ointment to the face and eyebrows for the AA. Maintenance of terminal hair within a region of topically treated psoriasis on the forearm persisted at the 2-month follow-up despite complete clearance of the corresponding psoriatic plaque. A small psoriatic plaque on the scalp cleared early with topical therapy without noticeable hair regrowth. The patient subsequently was started on contact immunotherapy with SADBE and intralesional triamcinolone acetonide for the scalp alopecia without satisfactory response. He decided to discontinue further attempts at treating the alopecia and requested to be restarted on etanercept therapy for recalcitrant psoriatic plaques. His psoriasis responded well to this therapy and he continues to be followed in our psoriasis clinic. One year after clearance of the treated psoriatic plaques, the corresponding terminal hairs persist.

Contact immunotherapy, most commonly with diphenylcyclopropenone or SADBE, is reported to have a 50% to 60% success rate in extensive AA, with a broad range of 9% to 87%¹⁷; however, randomized controlled trials testing the efficacy of contact immunotherapy are lacking. Although the mechanism of action of these topical sensitizers is not clearly delineated, it has been postulated that by inducing a new type of inflammatory response in the region, the immunologic milieu is changed, allowing the hair to grow. Some proposed mechanisms include promoting perifollicular lymphocyte apoptosis, preventing new recruitment of autoreactive lymphocytes, and allowing for the correction of aberrant major histocompatibility complex expression on the hair matrix epithelium to regain follicle immune privilege.^18-20

Iatrogenic immunotherapy may work analogously to the natural immune system deviation demonstrated in our patient. Psoriasis and AA are believed to form competing immune cells and cytokine milieus, thus explaining how an individual with AA could regain normal hair growth in areas of psoriasis.^15,16 The Renbök phenomenon, or reverse Köbner phenomenon, coined by Happle et al¹³ can be used to describe both the iatrogenic and natural cases of dermatologic disease improvement in response to secondary insults.¹⁴

A complex cascade of immune cells and cytokines coordinate AA pathogenesis. In the acute stage of AA, an inflammatory infiltrate of CD4⁺ T cells, CD8⁺ T cells, and antigen-presenting cells target anagen phase follicles, with a higher CD4⁺:CD8⁺ ratio in clinically active disease.^21-23 Subcutaneous injections of either CD4⁺ or CD8⁺ lymphocyte subsets from mice with AA into normal-haired mice induces disease. However, CD8⁺ T cell injections rapidly produce apparent hair loss, whereas CD4⁺ T cells cause hair loss after several weeks, suggesting that CD8⁺ T cells directly modulate AA hair loss and CD4⁺ T cells act as an aide.²⁴ The growth, differentiation, and survival of CD8⁺ T cells are stimulated by IL-2 and IFN-γ. Alopecia areata biopsies demonstrate a prevalence of T_H1 cytokines, and patients with localized AA, alopecia totalis, and AU have notably higher serum IFN-γ levels compared to controls.²⁵ In murine models, IL-1α and IL-1β increase during the catagen phase of the hair cycle and peak during the telogen phase.²⁶ Excessive IL-1β expression is detected in the early stages of human disease, and certain IL-1β polymorphisms are associated with severe forms of AA.²⁶ The role of tumor necrosis factor (TNF) α in AA is not well understood. In vitro studies show it inhibits hair growth, suggesting the cytokine may play a role in AA.²⁷ However, anti–TNF-α therapy is not effective in AA, and case reports propose these therapies rarely induce AA.^28-31

The T_H1 response is likewise critical to psoriatic plaque development. IFN-γ and TNF-α are overexpressed in psoriatic plaques.³² IFN-γ has an antiproliferative and differentiation-inducing effect on normal keratinocytes, but psoriatic epithelial cells in vitro respond differently to the cytokine with a notably diminished growth inhibition.^33,34 One explanation for the role of IFN-γ is that it stimulates dendritic cells to produce IL-1 and IL-23.³⁵ IL-23 activates T_H17 cells³⁶; T_H1 and T_H17 conditions produce IL-22 whose serum level correlates with disease severity.^37-39 IL-22 induces keratinocyte proliferation and migration and inhibits keratinocyte differentiation, helping account for hallmarks of the disease.⁴⁰ Patients with psoriasis have increased levels of T_H1, T_H17, and T_H22 cells, as well as their associated cytokines, in the skin and blood compared to controls.^{4,11,32,39,41}

Alopecia areata and psoriasis are regulated by complex and still not entirely understood immune interactions. The fact that many of the same therapies are used to treat both diseases emphasizes both their overlapping characteristics and the lack of targeted therapy. It is unclear if and how the topical or systemic therapies used in our patient to treat one disease affected the natural history of the other condition. It is important to highlight, however, that the patient had not been treated for months when he developed the psoriatic plaques with hair regrowth. Other case reports also document hair regrowth in untreated plaques,^13,16 making it unlikely to be a side effect of the medication regimen. For both psoriasis and AA, the immune cell composition and cytokine levels in the skin or serum vary throughout a patient’s disease course depending on severity of disease or response to treatment.^6,39,42,43 Therefore, we hypothesize that the 2 conditions interact in a similarly distinct manner based on each disease’s stage and intensity in the patient. Both our patient’s course thus far and the various presentations described by other groups support this hypothesis. Our patient had a small region of psoriasis on the scalp that cleared without any terminal hair growth. He also had larger plaques on the forearms that developed hair growth most predominantly within the thicker regions of the plaques. His unique presentation highlights the fluidity of the immune factors driving psoriasis vulgaris and AA.

To the Editor:

Both alopecia areata (AA) and psoriasis vulgaris are chronic relapsing autoimmune diseases, with AA causing nonscarring hair loss in approximately 0.1% to 0.2%¹ of the population with a lifetime risk of 1.7%,² and psoriasis more broadly impacting 1.5% to 2% of the population.³ The helper T cell (T_H1) cytokine milieu is pathogenic in both conditions.^4-6 IFN-γ knockout mice, unlike their wild-type counterparts, do not exhibit AA.⁷ Psoriasis is notably improved by IL-10 injections, which dampen the T_H1 response.⁸ Distinct from AA, T_H17 and T_H22 cells have been implicated as key players in psoriasis pathogenesis, along with the associated IL-17 and IL-22 cytokines.^9-12

Few cases of patients with concurrent AA and psoriasis have been described. Interestingly, these cases document normal hair regrowth in the areas of psoriasis.^13-16 These cases may offer unique insight into the immune factors driving each disease. We describe a case of a man with both alopecia universalis (AU) and psoriasis who developed hair regrowth in some of the psoriatic plaques.

A 34-year-old man with concurrent AU and psoriasis who had not used any systemic or topical medication for either condition in the last year presented to our clinic seeking treatment. The patient had a history of alopecia totalis as a toddler that completely resolved by 4 years of age with the use of squaric acid dibutylester (SADBE). At 31 years of age, the alopecia recurred and was localized to the scalp. It was partially responsive to intralesional triamcinolone acetonide. The patient’s alopecia worsened over the 2 years following recurrence, ultimately progressing to AU. Two months after the alopecia recurrence, he developed the first psoriatic plaques. As the plaque psoriasis progressed, systemic therapy was initiated, first methotrexate and then etanercept. Shortly after developing AU, he lost his health insurance and discontinued all therapy. The patient’s psoriasis began to recur approximately 3 months after stopping etanercept. He was not using any other psoriasis medications. At that time, he noted terminal hair regrowth within some of the psoriatic plaques. No terminal hairs grew outside of the psoriatic plaques, and all regions with growth had previously been without hair for an extended period of time. The patient presented to our clinic approximately 1 year later. He had no other medical conditions and no relevant family history.

On initial physical examination, he had nonscarring hair loss involving nearly 100% of the body with psoriatic plaques on approximately 30% of the body surface area. Regions of terminal hair growth were confined to some but not all of the psoriatic plaques (Figure). Interestingly, the terminal hairs were primarily localized to the thickest central regions of the plaques. The patient’s psoriasis was treated with a combination of topical clobetasol and calcipotriene. In addition, he was started on tacrolimus ointment to the face and eyebrows for the AA. Maintenance of terminal hair within a region of topically treated psoriasis on the forearm persisted at the 2-month follow-up despite complete clearance of the corresponding psoriatic plaque. A small psoriatic plaque on the scalp cleared early with topical therapy without noticeable hair regrowth. The patient subsequently was started on contact immunotherapy with SADBE and intralesional triamcinolone acetonide for the scalp alopecia without satisfactory response. He decided to discontinue further attempts at treating the alopecia and requested to be restarted on etanercept therapy for recalcitrant psoriatic plaques. His psoriasis responded well to this therapy and he continues to be followed in our psoriasis clinic. One year after clearance of the treated psoriatic plaques, the corresponding terminal hairs persist.

Contact immunotherapy, most commonly with diphenylcyclopropenone or SADBE, is reported to have a 50% to 60% success rate in extensive AA, with a broad range of 9% to 87%¹⁷; however, randomized controlled trials testing the efficacy of contact immunotherapy are lacking. Although the mechanism of action of these topical sensitizers is not clearly delineated, it has been postulated that by inducing a new type of inflammatory response in the region, the immunologic milieu is changed, allowing the hair to grow. Some proposed mechanisms include promoting perifollicular lymphocyte apoptosis, preventing new recruitment of autoreactive lymphocytes, and allowing for the correction of aberrant major histocompatibility complex expression on the hair matrix epithelium to regain follicle immune privilege.^18-20

Iatrogenic immunotherapy may work analogously to the natural immune system deviation demonstrated in our patient. Psoriasis and AA are believed to form competing immune cells and cytokine milieus, thus explaining how an individual with AA could regain normal hair growth in areas of psoriasis.^15,16 The Renbök phenomenon, or reverse Köbner phenomenon, coined by Happle et al¹³ can be used to describe both the iatrogenic and natural cases of dermatologic disease improvement in response to secondary insults.¹⁴

A complex cascade of immune cells and cytokines coordinate AA pathogenesis. In the acute stage of AA, an inflammatory infiltrate of CD4⁺ T cells, CD8⁺ T cells, and antigen-presenting cells target anagen phase follicles, with a higher CD4⁺:CD8⁺ ratio in clinically active disease.^21-23 Subcutaneous injections of either CD4⁺ or CD8⁺ lymphocyte subsets from mice with AA into normal-haired mice induces disease. However, CD8⁺ T cell injections rapidly produce apparent hair loss, whereas CD4⁺ T cells cause hair loss after several weeks, suggesting that CD8⁺ T cells directly modulate AA hair loss and CD4⁺ T cells act as an aide.²⁴ The growth, differentiation, and survival of CD8⁺ T cells are stimulated by IL-2 and IFN-γ. Alopecia areata biopsies demonstrate a prevalence of T_H1 cytokines, and patients with localized AA, alopecia totalis, and AU have notably higher serum IFN-γ levels compared to controls.²⁵ In murine models, IL-1α and IL-1β increase during the catagen phase of the hair cycle and peak during the telogen phase.²⁶ Excessive IL-1β expression is detected in the early stages of human disease, and certain IL-1β polymorphisms are associated with severe forms of AA.²⁶ The role of tumor necrosis factor (TNF) α in AA is not well understood. In vitro studies show it inhibits hair growth, suggesting the cytokine may play a role in AA.²⁷ However, anti–TNF-α therapy is not effective in AA, and case reports propose these therapies rarely induce AA.^28-31

The T_H1 response is likewise critical to psoriatic plaque development. IFN-γ and TNF-α are overexpressed in psoriatic plaques.³² IFN-γ has an antiproliferative and differentiation-inducing effect on normal keratinocytes, but psoriatic epithelial cells in vitro respond differently to the cytokine with a notably diminished growth inhibition.^33,34 One explanation for the role of IFN-γ is that it stimulates dendritic cells to produce IL-1 and IL-23.³⁵ IL-23 activates T_H17 cells³⁶; T_H1 and T_H17 conditions produce IL-22 whose serum level correlates with disease severity.^37-39 IL-22 induces keratinocyte proliferation and migration and inhibits keratinocyte differentiation, helping account for hallmarks of the disease.⁴⁰ Patients with psoriasis have increased levels of T_H1, T_H17, and T_H22 cells, as well as their associated cytokines, in the skin and blood compared to controls.^{4,11,32,39,41}

Alopecia areata and psoriasis are regulated by complex and still not entirely understood immune interactions. The fact that many of the same therapies are used to treat both diseases emphasizes both their overlapping characteristics and the lack of targeted therapy. It is unclear if and how the topical or systemic therapies used in our patient to treat one disease affected the natural history of the other condition. It is important to highlight, however, that the patient had not been treated for months when he developed the psoriatic plaques with hair regrowth. Other case reports also document hair regrowth in untreated plaques,^13,16 making it unlikely to be a side effect of the medication regimen. For both psoriasis and AA, the immune cell composition and cytokine levels in the skin or serum vary throughout a patient’s disease course depending on severity of disease or response to treatment.^6,39,42,43 Therefore, we hypothesize that the 2 conditions interact in a similarly distinct manner based on each disease’s stage and intensity in the patient. Both our patient’s course thus far and the various presentations described by other groups support this hypothesis. Our patient had a small region of psoriasis on the scalp that cleared without any terminal hair growth. He also had larger plaques on the forearms that developed hair growth most predominantly within the thicker regions of the plaques. His unique presentation highlights the fluidity of the immune factors driving psoriasis vulgaris and AA.

To the Editor:

Both alopecia areata (AA) and psoriasis vulgaris are chronic relapsing autoimmune diseases, with AA causing nonscarring hair loss in approximately 0.1% to 0.2%¹ of the population with a lifetime risk of 1.7%,² and psoriasis more broadly impacting 1.5% to 2% of the population.³ The helper T cell (T_H1) cytokine milieu is pathogenic in both conditions.^4-6 IFN-γ knockout mice, unlike their wild-type counterparts, do not exhibit AA.⁷ Psoriasis is notably improved by IL-10 injections, which dampen the T_H1 response.⁸ Distinct from AA, T_H17 and T_H22 cells have been implicated as key players in psoriasis pathogenesis, along with the associated IL-17 and IL-22 cytokines.^9-12

Few cases of patients with concurrent AA and psoriasis have been described. Interestingly, these cases document normal hair regrowth in the areas of psoriasis.^13-16 These cases may offer unique insight into the immune factors driving each disease. We describe a case of a man with both alopecia universalis (AU) and psoriasis who developed hair regrowth in some of the psoriatic plaques.

A 34-year-old man with concurrent AU and psoriasis who had not used any systemic or topical medication for either condition in the last year presented to our clinic seeking treatment. The patient had a history of alopecia totalis as a toddler that completely resolved by 4 years of age with the use of squaric acid dibutylester (SADBE). At 31 years of age, the alopecia recurred and was localized to the scalp. It was partially responsive to intralesional triamcinolone acetonide. The patient’s alopecia worsened over the 2 years following recurrence, ultimately progressing to AU. Two months after the alopecia recurrence, he developed the first psoriatic plaques. As the plaque psoriasis progressed, systemic therapy was initiated, first methotrexate and then etanercept. Shortly after developing AU, he lost his health insurance and discontinued all therapy. The patient’s psoriasis began to recur approximately 3 months after stopping etanercept. He was not using any other psoriasis medications. At that time, he noted terminal hair regrowth within some of the psoriatic plaques. No terminal hairs grew outside of the psoriatic plaques, and all regions with growth had previously been without hair for an extended period of time. The patient presented to our clinic approximately 1 year later. He had no other medical conditions and no relevant family history.

On initial physical examination, he had nonscarring hair loss involving nearly 100% of the body with psoriatic plaques on approximately 30% of the body surface area. Regions of terminal hair growth were confined to some but not all of the psoriatic plaques (Figure). Interestingly, the terminal hairs were primarily localized to the thickest central regions of the plaques. The patient’s psoriasis was treated with a combination of topical clobetasol and calcipotriene. In addition, he was started on tacrolimus ointment to the face and eyebrows for the AA. Maintenance of terminal hair within a region of topically treated psoriasis on the forearm persisted at the 2-month follow-up despite complete clearance of the corresponding psoriatic plaque. A small psoriatic plaque on the scalp cleared early with topical therapy without noticeable hair regrowth. The patient subsequently was started on contact immunotherapy with SADBE and intralesional triamcinolone acetonide for the scalp alopecia without satisfactory response. He decided to discontinue further attempts at treating the alopecia and requested to be restarted on etanercept therapy for recalcitrant psoriatic plaques. His psoriasis responded well to this therapy and he continues to be followed in our psoriasis clinic. One year after clearance of the treated psoriatic plaques, the corresponding terminal hairs persist.

Contact immunotherapy, most commonly with diphenylcyclopropenone or SADBE, is reported to have a 50% to 60% success rate in extensive AA, with a broad range of 9% to 87%¹⁷; however, randomized controlled trials testing the efficacy of contact immunotherapy are lacking. Although the mechanism of action of these topical sensitizers is not clearly delineated, it has been postulated that by inducing a new type of inflammatory response in the region, the immunologic milieu is changed, allowing the hair to grow. Some proposed mechanisms include promoting perifollicular lymphocyte apoptosis, preventing new recruitment of autoreactive lymphocytes, and allowing for the correction of aberrant major histocompatibility complex expression on the hair matrix epithelium to regain follicle immune privilege.^18-20

Iatrogenic immunotherapy may work analogously to the natural immune system deviation demonstrated in our patient. Psoriasis and AA are believed to form competing immune cells and cytokine milieus, thus explaining how an individual with AA could regain normal hair growth in areas of psoriasis.^15,16 The Renbök phenomenon, or reverse Köbner phenomenon, coined by Happle et al¹³ can be used to describe both the iatrogenic and natural cases of dermatologic disease improvement in response to secondary insults.¹⁴

A complex cascade of immune cells and cytokines coordinate AA pathogenesis. In the acute stage of AA, an inflammatory infiltrate of CD4⁺ T cells, CD8⁺ T cells, and antigen-presenting cells target anagen phase follicles, with a higher CD4⁺:CD8⁺ ratio in clinically active disease.^21-23 Subcutaneous injections of either CD4⁺ or CD8⁺ lymphocyte subsets from mice with AA into normal-haired mice induces disease. However, CD8⁺ T cell injections rapidly produce apparent hair loss, whereas CD4⁺ T cells cause hair loss after several weeks, suggesting that CD8⁺ T cells directly modulate AA hair loss and CD4⁺ T cells act as an aide.²⁴ The growth, differentiation, and survival of CD8⁺ T cells are stimulated by IL-2 and IFN-γ. Alopecia areata biopsies demonstrate a prevalence of T_H1 cytokines, and patients with localized AA, alopecia totalis, and AU have notably higher serum IFN-γ levels compared to controls.²⁵ In murine models, IL-1α and IL-1β increase during the catagen phase of the hair cycle and peak during the telogen phase.²⁶ Excessive IL-1β expression is detected in the early stages of human disease, and certain IL-1β polymorphisms are associated with severe forms of AA.²⁶ The role of tumor necrosis factor (TNF) α in AA is not well understood. In vitro studies show it inhibits hair growth, suggesting the cytokine may play a role in AA.²⁷ However, anti–TNF-α therapy is not effective in AA, and case reports propose these therapies rarely induce AA.^28-31

The T_H1 response is likewise critical to psoriatic plaque development. IFN-γ and TNF-α are overexpressed in psoriatic plaques.³² IFN-γ has an antiproliferative and differentiation-inducing effect on normal keratinocytes, but psoriatic epithelial cells in vitro respond differently to the cytokine with a notably diminished growth inhibition.^33,34 One explanation for the role of IFN-γ is that it stimulates dendritic cells to produce IL-1 and IL-23.³⁵ IL-23 activates T_H17 cells³⁶; T_H1 and T_H17 conditions produce IL-22 whose serum level correlates with disease severity.^37-39 IL-22 induces keratinocyte proliferation and migration and inhibits keratinocyte differentiation, helping account for hallmarks of the disease.⁴⁰ Patients with psoriasis have increased levels of T_H1, T_H17, and T_H22 cells, as well as their associated cytokines, in the skin and blood compared to controls.^{4,11,32,39,41}

Alopecia areata and psoriasis are regulated by complex and still not entirely understood immune interactions. The fact that many of the same therapies are used to treat both diseases emphasizes both their overlapping characteristics and the lack of targeted therapy. It is unclear if and how the topical or systemic therapies used in our patient to treat one disease affected the natural history of the other condition. It is important to highlight, however, that the patient had not been treated for months when he developed the psoriatic plaques with hair regrowth. Other case reports also document hair regrowth in untreated plaques,^13,16 making it unlikely to be a side effect of the medication regimen. For both psoriasis and AA, the immune cell composition and cytokine levels in the skin or serum vary throughout a patient’s disease course depending on severity of disease or response to treatment.^6,39,42,43 Therefore, we hypothesize that the 2 conditions interact in a similarly distinct manner based on each disease’s stage and intensity in the patient. Both our patient’s course thus far and the various presentations described by other groups support this hypothesis. Our patient had a small region of psoriasis on the scalp that cleared without any terminal hair growth. He also had larger plaques on the forearms that developed hair growth most predominantly within the thicker regions of the plaques. His unique presentation highlights the fluidity of the immune factors driving psoriasis vulgaris and AA.

Onychomycosis is a common progressive fungal infection of the nail bed, matrix, or plate leading to destruction and deformity of the toenails and fingernails.^1,2 It represents up to 50% of all nail disorders^1,3 with a notable increasing prevalence in the United States.^4-6

Latinos represent the largest ethnic minority group in the United States,⁷ which is growing rapidly through immigration, particularly in the southern United States. Prevalence data are limited. An incidence of 9.3% secondary to dermatophytes was recorded in a dermatology clinic setting (N=2000).⁸ Onychomycosis was reported in 31.9% of a group of Latino immigrants in North Carolina (N=518), with higher prevalence in poultry workers, possibly due to the work environment.⁹

Efinaconazole solution 10% was shown to be well tolerated and more effective than a vehicle in a phase 2 study in Mexico.¹⁰ Two identical phase 3 studies of 1655 participants assessed the safety and efficacy of efinaconazole solution 10% in the treatment of onychomycosis.¹¹ This post hoc analysis compares the data for Latino versus non-Latino populations.

Methods

We evaluated the results of 2 multicenter, randomized, double-blind, vehicle-controlled studies that included a total of 1655 participants with mild to moderate toenail onychomycosis (20%–50% clinical involvement). Participants were randomized to efinaconazole solu-tion 10% or vehicle once daily (3:1) for 48 weeks with a 4-week posttreatment follow-up period.¹¹

Our post hoc analysis included 270 Latino patients, defined as an individual of Cuban, Mexican, Puerto Rican, or South or Central American origin or other Latino culture, regardless of race. In addition, data were compared to the 1380 non-Latino patients in the 2 studies. Patients who were randomized in error and never received treatment were excluded from the intention-to-treat analysis.

Efficacy Evaluation

The primary efficacy end point was complete cure rate (0% clinical involvement of target toenail, and both negative potassium hydroxide examination and fungal culture) at week 52. Secondary end points included mycologic cure, complete/almost complete cure (≤5% clinical involvement of target toenail, mycologic cure), and treatment success (≤10% clinical involvement of target toenail) at week 52.

Safety Evaluation

Safety assessments included monitoring and recording of adverse events (AEs) at every postbaseline study visit through week 52. All AEs were classified using the Medical Dictionary for Regulatory Activities (version 12.1). Treatment-emergent AEs (ie, events that began after the first application of study drug) that occurred during the study were summarized for each treatment group by the number of patients reporting each event, as well as by system organ class, preferred term, severity, seriousness, and relationship to the study drug.

Results

A total of 270 Latino participants with toenail onychomycosis (efinaconazole solution 10%, n=193; vehicle, n=77) were included in our study. The mean age of participants at baseline was 45.9 years. They were predominantly male (69.6%) and white Latinos (91.1%). The mean area of target toenail involvement was 36.6%, and the mean number of affected nontarget toenails was 2.5. Latino participants tended to be younger than non-Latino participants (45.9 vs 52.6 years), with a higher proportion of females (30.4% vs 21.3%). Disease severity was similar in both populations. Diabetes was reported in 7.0% and 6.7% of Latino and non-Latino participants, respectively, and mean weight was 83.6 and 86.6 kg, respectively.

Primary Efficacy End Points (Observed Case [OC])

At week 52, 25.6% of Latino participants in the efinaconazole group achieved complete cure versus 0% in the vehicle group (P<.001)(Figure 1). The efficacy of efinaconazole was statistically superior in Latino participants versus non-Latino participants (17.2% [P=.012]). The net effect (calculated by active treatment minus vehicle) for Latino participants also was superior to non-Latino participants (25.6% vs 11.6%).

Secondary Efficacy End Points (OC)

At week 52, 61.5% of Latino participants in the efina-conazole group achieved mycologic cure versus 15.3% in the vehicle group (P<.001)(Figure 2). The net effect for Latino participants was superior to non-Latino participants (46.2% vs 38.5%). More Latino participants in the efinaconazole group compared to vehicle group achieved complete/almost complete cure (32.7% vs 1.7%) or treatment success (49.4% vs 5.1%)(all P<.001)(Figure 3). Although there was no significant difference between the 2 groups for secondary efficacy end points, the net effect of efinaconazole was greater for all end points.

Safety

Adverse event rates were higher in the efinaconazole group than the vehicle group (65.3% vs 54.4%) and were similar in both populations; they were generally mild (61.8% vs 54.5%) or moderate (35.3% vs 45.5%) in severity, not related to study medication (96.8% vs 98.0%), and resolved without sequelae. Only 3 Latino participants (1.6%) discontinued efinaconazole treatment compared to 29 (2.8%) in the non-Latino population.

Comment

With the continued growth of the Latino population in the United States and likely higher prevalence of onychomycosis,⁹ this post hoc analysis provides important insights into treatment of onychomycosis in this patient population.

Efinaconazole solution 10% was significantly more effective than vehicle in the Latino population (P<.001) and also appeared significantly more effective than the non-Latino population across the 2 phase 3 studies (P=.012). Interestingly, complete cure rates (25.6%) were identical to those reported in the phase 2 study of Mexican patients treated with efinaconazole for 36 weeks.¹⁰ Specific data with other topical therapies, such as tavaborole, in Latino patients are not available. One phase 3 study of tavaborole for onychomycosis included 89 Mexican patients (15% of the total study population), but complete cure rates for the overall active treatment group were higher in a second phase 3 study (6.5% vs 9.1%) that did not include participants outside the United States or Canada.¹²

It is not clear why phase 3 efficacy results with efinaconazole appear better in the Latino population. There are a number of predisposing factors for onychomycosis that are important treatment considerations in Latinos. Obesity is an important factor in the development of onychomycosis,¹³ with more than 42% of Latino adults in the United States reportedly obese compared to 32.6% of non-Latino adults.¹⁴ Obese patients reportedly have shown a poorer response to efinaconazole treatment¹⁵; however, in our analysis, the mean weight of the 2 subpopulations was similar at baseline. Diabetes also is associated with an increased risk for onychomycosis^16,17 and may be a more important issue in Latinos perhaps due to differences in health care access, social and cultural factors, and/or genetics, as well as the greater incidence of obesity. Prior reports suggest the efficacy of efinaconazole is not substantially influenced by the presence of diabetes,¹⁸ and in our 2 subpopulations, baseline incidence of coexisting diabetes was similar. These factors are unlikely to account for the better treatment success seen in our analysis. Efinaconazole has been reported to be more effective in females,¹⁹ though the reasons are less clear. The higher proportion of female Latinos (30.4% vs 21.3%) in our study may have had an impact on the results reported, though this baseline characteristic cannot be considered in isolation.

When considering the net effect (active minus vehicle), the apparent benefits of efinaconazole in Latino patients with onychomycosis were more marked. Vehicle complete cure rates at week 52 were 0% compared with 5.6% of non-Latino participants. Vehicle cure rates in randomized controlled trials of toenail onychomycosis are relatively low and appear to be independent of the study characteristics.²⁰ Vehicle cure rates of 2 topical treatments—efinaconazole and tavaborole—reported in their 2 respective phase 3 studies were 3.3% and 5.5% for efinaconzole¹¹ and 0.5% and 1.5% for tavaborole.¹² It has been suggested that the higher results seen with the efinaconazole vehicle relate to the formulation, though there is no reason to expect it to perform differently in a Latino population. It also has been suggested that baseline disease severity might impact vehicle treatment outcome.²⁰ In our analysis, the percentage affected nail at baseline was higher in the Latino participants treated with vehicle (38.9% vs 36.2%).

Although the overall level of AEs was similar in Latino versus non-Latino participants treated with efinaconazole, events were generally milder in the Latino subpopulation and fewer participants discontinued because of AEs.

Our study had a number of limitations. A study period of 52 weeks may be too brief to evaluate clinical cure in onychomycosis, as continued improvement could occur with either longer treatment or follow-up. Also, the pivotal studies were not set up to specifically study Latino participants; the demographics and study disposition may not be representative of the general Latino population.

Conclusion

Once-daily treatment with efinaconazole solution 10% may provide a useful topical option in the treatment of Latino patients with toenail onychomycosis.

Acknowledgment

The authors would like to thank Brian Bulley, MSc (Konic Limited, West Sussex, United Kingdom), for medical writing support. Valeant Pharmaceuticals North America LLC funded Konic Limited’s activities pertaining to this manuscript. Dr. Cook-Bolden did not receive funding or any form of compensation for authorship of this publication.

Onychomycosis is a common progressive fungal infection of the nail bed, matrix, or plate leading to destruction and deformity of the toenails and fingernails.^1,2 It represents up to 50% of all nail disorders^1,3 with a notable increasing prevalence in the United States.^4-6

Latinos represent the largest ethnic minority group in the United States,⁷ which is growing rapidly through immigration, particularly in the southern United States. Prevalence data are limited. An incidence of 9.3% secondary to dermatophytes was recorded in a dermatology clinic setting (N=2000).⁸ Onychomycosis was reported in 31.9% of a group of Latino immigrants in North Carolina (N=518), with higher prevalence in poultry workers, possibly due to the work environment.⁹

Efinaconazole solution 10% was shown to be well tolerated and more effective than a vehicle in a phase 2 study in Mexico.¹⁰ Two identical phase 3 studies of 1655 participants assessed the safety and efficacy of efinaconazole solution 10% in the treatment of onychomycosis.¹¹ This post hoc analysis compares the data for Latino versus non-Latino populations.

Methods

We evaluated the results of 2 multicenter, randomized, double-blind, vehicle-controlled studies that included a total of 1655 participants with mild to moderate toenail onychomycosis (20%–50% clinical involvement). Participants were randomized to efinaconazole solu-tion 10% or vehicle once daily (3:1) for 48 weeks with a 4-week posttreatment follow-up period.¹¹

Our post hoc analysis included 270 Latino patients, defined as an individual of Cuban, Mexican, Puerto Rican, or South or Central American origin or other Latino culture, regardless of race. In addition, data were compared to the 1380 non-Latino patients in the 2 studies. Patients who were randomized in error and never received treatment were excluded from the intention-to-treat analysis.

Efficacy Evaluation

The primary efficacy end point was complete cure rate (0% clinical involvement of target toenail, and both negative potassium hydroxide examination and fungal culture) at week 52. Secondary end points included mycologic cure, complete/almost complete cure (≤5% clinical involvement of target toenail, mycologic cure), and treatment success (≤10% clinical involvement of target toenail) at week 52.

Safety Evaluation

Safety assessments included monitoring and recording of adverse events (AEs) at every postbaseline study visit through week 52. All AEs were classified using the Medical Dictionary for Regulatory Activities (version 12.1). Treatment-emergent AEs (ie, events that began after the first application of study drug) that occurred during the study were summarized for each treatment group by the number of patients reporting each event, as well as by system organ class, preferred term, severity, seriousness, and relationship to the study drug.

Results

A total of 270 Latino participants with toenail onychomycosis (efinaconazole solution 10%, n=193; vehicle, n=77) were included in our study. The mean age of participants at baseline was 45.9 years. They were predominantly male (69.6%) and white Latinos (91.1%). The mean area of target toenail involvement was 36.6%, and the mean number of affected nontarget toenails was 2.5. Latino participants tended to be younger than non-Latino participants (45.9 vs 52.6 years), with a higher proportion of females (30.4% vs 21.3%). Disease severity was similar in both populations. Diabetes was reported in 7.0% and 6.7% of Latino and non-Latino participants, respectively, and mean weight was 83.6 and 86.6 kg, respectively.

Primary Efficacy End Points (Observed Case [OC])

At week 52, 25.6% of Latino participants in the efinaconazole group achieved complete cure versus 0% in the vehicle group (P<.001)(Figure 1). The efficacy of efinaconazole was statistically superior in Latino participants versus non-Latino participants (17.2% [P=.012]). The net effect (calculated by active treatment minus vehicle) for Latino participants also was superior to non-Latino participants (25.6% vs 11.6%).

Secondary Efficacy End Points (OC)

At week 52, 61.5% of Latino participants in the efina-conazole group achieved mycologic cure versus 15.3% in the vehicle group (P<.001)(Figure 2). The net effect for Latino participants was superior to non-Latino participants (46.2% vs 38.5%). More Latino participants in the efinaconazole group compared to vehicle group achieved complete/almost complete cure (32.7% vs 1.7%) or treatment success (49.4% vs 5.1%)(all P<.001)(Figure 3). Although there was no significant difference between the 2 groups for secondary efficacy end points, the net effect of efinaconazole was greater for all end points.

Safety

Adverse event rates were higher in the efinaconazole group than the vehicle group (65.3% vs 54.4%) and were similar in both populations; they were generally mild (61.8% vs 54.5%) or moderate (35.3% vs 45.5%) in severity, not related to study medication (96.8% vs 98.0%), and resolved without sequelae. Only 3 Latino participants (1.6%) discontinued efinaconazole treatment compared to 29 (2.8%) in the non-Latino population.

Comment

With the continued growth of the Latino population in the United States and likely higher prevalence of onychomycosis,⁹ this post hoc analysis provides important insights into treatment of onychomycosis in this patient population.

Efinaconazole solution 10% was significantly more effective than vehicle in the Latino population (P<.001) and also appeared significantly more effective than the non-Latino population across the 2 phase 3 studies (P=.012). Interestingly, complete cure rates (25.6%) were identical to those reported in the phase 2 study of Mexican patients treated with efinaconazole for 36 weeks.¹⁰ Specific data with other topical therapies, such as tavaborole, in Latino patients are not available. One phase 3 study of tavaborole for onychomycosis included 89 Mexican patients (15% of the total study population), but complete cure rates for the overall active treatment group were higher in a second phase 3 study (6.5% vs 9.1%) that did not include participants outside the United States or Canada.¹²

It is not clear why phase 3 efficacy results with efinaconazole appear better in the Latino population. There are a number of predisposing factors for onychomycosis that are important treatment considerations in Latinos. Obesity is an important factor in the development of onychomycosis,¹³ with more than 42% of Latino adults in the United States reportedly obese compared to 32.6% of non-Latino adults.¹⁴ Obese patients reportedly have shown a poorer response to efinaconazole treatment¹⁵; however, in our analysis, the mean weight of the 2 subpopulations was similar at baseline. Diabetes also is associated with an increased risk for onychomycosis^16,17 and may be a more important issue in Latinos perhaps due to differences in health care access, social and cultural factors, and/or genetics, as well as the greater incidence of obesity. Prior reports suggest the efficacy of efinaconazole is not substantially influenced by the presence of diabetes,¹⁸ and in our 2 subpopulations, baseline incidence of coexisting diabetes was similar. These factors are unlikely to account for the better treatment success seen in our analysis. Efinaconazole has been reported to be more effective in females,¹⁹ though the reasons are less clear. The higher proportion of female Latinos (30.4% vs 21.3%) in our study may have had an impact on the results reported, though this baseline characteristic cannot be considered in isolation.

When considering the net effect (active minus vehicle), the apparent benefits of efinaconazole in Latino patients with onychomycosis were more marked. Vehicle complete cure rates at week 52 were 0% compared with 5.6% of non-Latino participants. Vehicle cure rates in randomized controlled trials of toenail onychomycosis are relatively low and appear to be independent of the study characteristics.²⁰ Vehicle cure rates of 2 topical treatments—efinaconazole and tavaborole—reported in their 2 respective phase 3 studies were 3.3% and 5.5% for efinaconzole¹¹ and 0.5% and 1.5% for tavaborole.¹² It has been suggested that the higher results seen with the efinaconazole vehicle relate to the formulation, though there is no reason to expect it to perform differently in a Latino population. It also has been suggested that baseline disease severity might impact vehicle treatment outcome.²⁰ In our analysis, the percentage affected nail at baseline was higher in the Latino participants treated with vehicle (38.9% vs 36.2%).

Although the overall level of AEs was similar in Latino versus non-Latino participants treated with efinaconazole, events were generally milder in the Latino subpopulation and fewer participants discontinued because of AEs.

Our study had a number of limitations. A study period of 52 weeks may be too brief to evaluate clinical cure in onychomycosis, as continued improvement could occur with either longer treatment or follow-up. Also, the pivotal studies were not set up to specifically study Latino participants; the demographics and study disposition may not be representative of the general Latino population.

Conclusion

Once-daily treatment with efinaconazole solution 10% may provide a useful topical option in the treatment of Latino patients with toenail onychomycosis.

Acknowledgment

The authors would like to thank Brian Bulley, MSc (Konic Limited, West Sussex, United Kingdom), for medical writing support. Valeant Pharmaceuticals North America LLC funded Konic Limited’s activities pertaining to this manuscript. Dr. Cook-Bolden did not receive funding or any form of compensation for authorship of this publication.

Onychomycosis is a common progressive fungal infection of the nail bed, matrix, or plate leading to destruction and deformity of the toenails and fingernails.^1,2 It represents up to 50% of all nail disorders^1,3 with a notable increasing prevalence in the United States.^4-6

Latinos represent the largest ethnic minority group in the United States,⁷ which is growing rapidly through immigration, particularly in the southern United States. Prevalence data are limited. An incidence of 9.3% secondary to dermatophytes was recorded in a dermatology clinic setting (N=2000).⁸ Onychomycosis was reported in 31.9% of a group of Latino immigrants in North Carolina (N=518), with higher prevalence in poultry workers, possibly due to the work environment.⁹

Efinaconazole solution 10% was shown to be well tolerated and more effective than a vehicle in a phase 2 study in Mexico.¹⁰ Two identical phase 3 studies of 1655 participants assessed the safety and efficacy of efinaconazole solution 10% in the treatment of onychomycosis.¹¹ This post hoc analysis compares the data for Latino versus non-Latino populations.

Methods

We evaluated the results of 2 multicenter, randomized, double-blind, vehicle-controlled studies that included a total of 1655 participants with mild to moderate toenail onychomycosis (20%–50% clinical involvement). Participants were randomized to efinaconazole solu-tion 10% or vehicle once daily (3:1) for 48 weeks with a 4-week posttreatment follow-up period.¹¹

Our post hoc analysis included 270 Latino patients, defined as an individual of Cuban, Mexican, Puerto Rican, or South or Central American origin or other Latino culture, regardless of race. In addition, data were compared to the 1380 non-Latino patients in the 2 studies. Patients who were randomized in error and never received treatment were excluded from the intention-to-treat analysis.

Efficacy Evaluation

The primary efficacy end point was complete cure rate (0% clinical involvement of target toenail, and both negative potassium hydroxide examination and fungal culture) at week 52. Secondary end points included mycologic cure, complete/almost complete cure (≤5% clinical involvement of target toenail, mycologic cure), and treatment success (≤10% clinical involvement of target toenail) at week 52.

Safety Evaluation

Safety assessments included monitoring and recording of adverse events (AEs) at every postbaseline study visit through week 52. All AEs were classified using the Medical Dictionary for Regulatory Activities (version 12.1). Treatment-emergent AEs (ie, events that began after the first application of study drug) that occurred during the study were summarized for each treatment group by the number of patients reporting each event, as well as by system organ class, preferred term, severity, seriousness, and relationship to the study drug.

Results

A total of 270 Latino participants with toenail onychomycosis (efinaconazole solution 10%, n=193; vehicle, n=77) were included in our study. The mean age of participants at baseline was 45.9 years. They were predominantly male (69.6%) and white Latinos (91.1%). The mean area of target toenail involvement was 36.6%, and the mean number of affected nontarget toenails was 2.5. Latino participants tended to be younger than non-Latino participants (45.9 vs 52.6 years), with a higher proportion of females (30.4% vs 21.3%). Disease severity was similar in both populations. Diabetes was reported in 7.0% and 6.7% of Latino and non-Latino participants, respectively, and mean weight was 83.6 and 86.6 kg, respectively.

Primary Efficacy End Points (Observed Case [OC])

At week 52, 25.6% of Latino participants in the efinaconazole group achieved complete cure versus 0% in the vehicle group (P<.001)(Figure 1). The efficacy of efinaconazole was statistically superior in Latino participants versus non-Latino participants (17.2% [P=.012]). The net effect (calculated by active treatment minus vehicle) for Latino participants also was superior to non-Latino participants (25.6% vs 11.6%).

Secondary Efficacy End Points (OC)

At week 52, 61.5% of Latino participants in the efina-conazole group achieved mycologic cure versus 15.3% in the vehicle group (P<.001)(Figure 2). The net effect for Latino participants was superior to non-Latino participants (46.2% vs 38.5%). More Latino participants in the efinaconazole group compared to vehicle group achieved complete/almost complete cure (32.7% vs 1.7%) or treatment success (49.4% vs 5.1%)(all P<.001)(Figure 3). Although there was no significant difference between the 2 groups for secondary efficacy end points, the net effect of efinaconazole was greater for all end points.

Safety

Adverse event rates were higher in the efinaconazole group than the vehicle group (65.3% vs 54.4%) and were similar in both populations; they were generally mild (61.8% vs 54.5%) or moderate (35.3% vs 45.5%) in severity, not related to study medication (96.8% vs 98.0%), and resolved without sequelae. Only 3 Latino participants (1.6%) discontinued efinaconazole treatment compared to 29 (2.8%) in the non-Latino population.

Comment

With the continued growth of the Latino population in the United States and likely higher prevalence of onychomycosis,⁹ this post hoc analysis provides important insights into treatment of onychomycosis in this patient population.

Efinaconazole solution 10% was significantly more effective than vehicle in the Latino population (P<.001) and also appeared significantly more effective than the non-Latino population across the 2 phase 3 studies (P=.012). Interestingly, complete cure rates (25.6%) were identical to those reported in the phase 2 study of Mexican patients treated with efinaconazole for 36 weeks.¹⁰ Specific data with other topical therapies, such as tavaborole, in Latino patients are not available. One phase 3 study of tavaborole for onychomycosis included 89 Mexican patients (15% of the total study population), but complete cure rates for the overall active treatment group were higher in a second phase 3 study (6.5% vs 9.1%) that did not include participants outside the United States or Canada.¹²

It is not clear why phase 3 efficacy results with efinaconazole appear better in the Latino population. There are a number of predisposing factors for onychomycosis that are important treatment considerations in Latinos. Obesity is an important factor in the development of onychomycosis,¹³ with more than 42% of Latino adults in the United States reportedly obese compared to 32.6% of non-Latino adults.¹⁴ Obese patients reportedly have shown a poorer response to efinaconazole treatment¹⁵; however, in our analysis, the mean weight of the 2 subpopulations was similar at baseline. Diabetes also is associated with an increased risk for onychomycosis^16,17 and may be a more important issue in Latinos perhaps due to differences in health care access, social and cultural factors, and/or genetics, as well as the greater incidence of obesity. Prior reports suggest the efficacy of efinaconazole is not substantially influenced by the presence of diabetes,¹⁸ and in our 2 subpopulations, baseline incidence of coexisting diabetes was similar. These factors are unlikely to account for the better treatment success seen in our analysis. Efinaconazole has been reported to be more effective in females,¹⁹ though the reasons are less clear. The higher proportion of female Latinos (30.4% vs 21.3%) in our study may have had an impact on the results reported, though this baseline characteristic cannot be considered in isolation.

When considering the net effect (active minus vehicle), the apparent benefits of efinaconazole in Latino patients with onychomycosis were more marked. Vehicle complete cure rates at week 52 were 0% compared with 5.6% of non-Latino participants. Vehicle cure rates in randomized controlled trials of toenail onychomycosis are relatively low and appear to be independent of the study characteristics.²⁰ Vehicle cure rates of 2 topical treatments—efinaconazole and tavaborole—reported in their 2 respective phase 3 studies were 3.3% and 5.5% for efinaconzole¹¹ and 0.5% and 1.5% for tavaborole.¹² It has been suggested that the higher results seen with the efinaconazole vehicle relate to the formulation, though there is no reason to expect it to perform differently in a Latino population. It also has been suggested that baseline disease severity might impact vehicle treatment outcome.²⁰ In our analysis, the percentage affected nail at baseline was higher in the Latino participants treated with vehicle (38.9% vs 36.2%).

Although the overall level of AEs was similar in Latino versus non-Latino participants treated with efinaconazole, events were generally milder in the Latino subpopulation and fewer participants discontinued because of AEs.

Our study had a number of limitations. A study period of 52 weeks may be too brief to evaluate clinical cure in onychomycosis, as continued improvement could occur with either longer treatment or follow-up. Also, the pivotal studies were not set up to specifically study Latino participants; the demographics and study disposition may not be representative of the general Latino population.

Conclusion

Once-daily treatment with efinaconazole solution 10% may provide a useful topical option in the treatment of Latino patients with toenail onychomycosis.

Acknowledgment

The authors would like to thank Brian Bulley, MSc (Konic Limited, West Sussex, United Kingdom), for medical writing support. Valeant Pharmaceuticals North America LLC funded Konic Limited’s activities pertaining to this manuscript. Dr. Cook-Bolden did not receive funding or any form of compensation for authorship of this publication.

To improve patient care and outcomes, leading dermatologists offered their recommendations on dry cuticle products. Consideration must be given to:

• Aquaphor Healing Ointment
  Beiersdorf Inc.
  “Using this product several times daily works great.”—Gary Goldenberg, MD, New York, New York

• Elon Lanolin-Rich Nail Conditioner
  Dartmouth Pharmaceuticals
  “Dry cuticles often are accompanied by splitting, cracking, and peeling of the nails. I have found that with regular use of this product, the condition of the nail as well as the cuticle can improve dramatically, leading to smoother, stronger cuticles and nails.”—Jeannette Graf, MD, New York, New York

• Petrolatum or Olive Oil
  Manufacturers vary
  “Apply petrolatum or olive oil to the fingertips after soaking for 5 to 10 minutes in lukewarm water, then wear nitrile gloves for an hour. Patients should then wipe off the excess and put on cotton gloves overnight.”—Larisa Ravitskiy, MD, Gahanna, Ohio

Cutis invites readers to send us their recommendations. Athlete’s foot treatments, as well as products for dry cuticles, hyperhidrosis, and sensitive skin will be featured in upcoming editions of Cosmetic Corner. Please e-mail your recommendation(s) to the Editorial Office.

Disclaimer: Opinions expressed herein do not necessarily reflect those of Cutis or Frontline Medical Communications Inc. and shall not be used for product endorsement purposes. Any reference made to a specific commercial product does not indicate or imply that Cutis or Frontline Medical Communications Inc. endorses, recommends, or favors the product mentioned. No guarantee is given to the effects of recommended products.

[polldaddy:9711250]

To improve patient care and outcomes, leading dermatologists offered their recommendations on dry cuticle products. Consideration must be given to:

• Aquaphor Healing Ointment
  Beiersdorf Inc.
  “Using this product several times daily works great.”—Gary Goldenberg, MD, New York, New York

• Elon Lanolin-Rich Nail Conditioner
  Dartmouth Pharmaceuticals
  “Dry cuticles often are accompanied by splitting, cracking, and peeling of the nails. I have found that with regular use of this product, the condition of the nail as well as the cuticle can improve dramatically, leading to smoother, stronger cuticles and nails.”—Jeannette Graf, MD, New York, New York

• Petrolatum or Olive Oil
  Manufacturers vary
  “Apply petrolatum or olive oil to the fingertips after soaking for 5 to 10 minutes in lukewarm water, then wear nitrile gloves for an hour. Patients should then wipe off the excess and put on cotton gloves overnight.”—Larisa Ravitskiy, MD, Gahanna, Ohio

Cutis invites readers to send us their recommendations. Athlete’s foot treatments, as well as products for dry cuticles, hyperhidrosis, and sensitive skin will be featured in upcoming editions of Cosmetic Corner. Please e-mail your recommendation(s) to the Editorial Office.

Disclaimer: Opinions expressed herein do not necessarily reflect those of Cutis or Frontline Medical Communications Inc. and shall not be used for product endorsement purposes. Any reference made to a specific commercial product does not indicate or imply that Cutis or Frontline Medical Communications Inc. endorses, recommends, or favors the product mentioned. No guarantee is given to the effects of recommended products.

[polldaddy:9711250]

To improve patient care and outcomes, leading dermatologists offered their recommendations on dry cuticle products. Consideration must be given to:

• Aquaphor Healing Ointment
  Beiersdorf Inc.
  “Using this product several times daily works great.”—Gary Goldenberg, MD, New York, New York

• Elon Lanolin-Rich Nail Conditioner
  Dartmouth Pharmaceuticals
  “Dry cuticles often are accompanied by splitting, cracking, and peeling of the nails. I have found that with regular use of this product, the condition of the nail as well as the cuticle can improve dramatically, leading to smoother, stronger cuticles and nails.”—Jeannette Graf, MD, New York, New York

• Petrolatum or Olive Oil
  Manufacturers vary
  “Apply petrolatum or olive oil to the fingertips after soaking for 5 to 10 minutes in lukewarm water, then wear nitrile gloves for an hour. Patients should then wipe off the excess and put on cotton gloves overnight.”—Larisa Ravitskiy, MD, Gahanna, Ohio

Cutis invites readers to send us their recommendations. Athlete’s foot treatments, as well as products for dry cuticles, hyperhidrosis, and sensitive skin will be featured in upcoming editions of Cosmetic Corner. Please e-mail your recommendation(s) to the Editorial Office.

Disclaimer: Opinions expressed herein do not necessarily reflect those of Cutis or Frontline Medical Communications Inc. and shall not be used for product endorsement purposes. Any reference made to a specific commercial product does not indicate or imply that Cutis or Frontline Medical Communications Inc. endorses, recommends, or favors the product mentioned. No guarantee is given to the effects of recommended products.

[polldaddy:9711250]

ORLANDO – A novel orally administered antifungal showed a favorable safety and efficacy profile in the treatment of distal lateral subungual onychomycosis, in a phase IIB study presented at the annual meeting of the American Academy of Dermatology.

In the RENOVATE (Restoring Nail: An Oral VT-1161 Tablet Evaluation) study, a randomized, double-blind, placebo-controlled, dose-ranging trial, 259 adults with moderate to severe distal lateral subungual onychomycosis of the large toenail were assigned to either one of four treatment arms. They were given the antifungal, currently named VT-1161, a selective CYP51 inhibitor, at doses of 300 mg or 600 mg once weekly for 10 or 22 weeks, after receiving daily loading doses for the initial 2 weeks. The trial evaluated two dose levels of VT-1161 (300 mg and 600 mg) administered once weekly for either 10 or 22 weeks following an initial 2-week, once-daily loading dose period.

At baseline, the average involvement of the large toenail was 46%, with an average of 4.6 toenails affected. In the intent-to-treat analysis, at 48 weeks, complete cure rates in the four study drug arms ranged from 32% to 42%, compared with 0% in the placebo arm.

Amir Tavakkol, PhD, chief development officer at Viamet Pharmaceuticals, which is developing VT01161, presented the study findings during a late breaking clinical session at the meeting.

Adverse event rates and discontinuation rates were comparable to placebo through week 60, with no patients discontinuing due to any laboratory abnormalities. Nausea and muscle spasms were the most commonly reported adverse events, which Dr. Tavakkol said seemed to occur in patients given the higher doses. VT-1161 is also being studied for treatment of vulvovaginal candidiasis. In October 2016, the FDA granted the drug Qualified Infectious Disease Product and Fast Track designations for the treatment of recurrent vulvovaginal candidiasis, according to the company.

Viamet sponsored the study and Dr. Tavakkol is an employee of the company.

[email protected]

On Twitter @whitneymcknight

ORLANDO – A novel orally administered antifungal showed a favorable safety and efficacy profile in the treatment of distal lateral subungual onychomycosis, in a phase IIB study presented at the annual meeting of the American Academy of Dermatology.

In the RENOVATE (Restoring Nail: An Oral VT-1161 Tablet Evaluation) study, a randomized, double-blind, placebo-controlled, dose-ranging trial, 259 adults with moderate to severe distal lateral subungual onychomycosis of the large toenail were assigned to either one of four treatment arms. They were given the antifungal, currently named VT-1161, a selective CYP51 inhibitor, at doses of 300 mg or 600 mg once weekly for 10 or 22 weeks, after receiving daily loading doses for the initial 2 weeks. The trial evaluated two dose levels of VT-1161 (300 mg and 600 mg) administered once weekly for either 10 or 22 weeks following an initial 2-week, once-daily loading dose period.

At baseline, the average involvement of the large toenail was 46%, with an average of 4.6 toenails affected. In the intent-to-treat analysis, at 48 weeks, complete cure rates in the four study drug arms ranged from 32% to 42%, compared with 0% in the placebo arm.

Amir Tavakkol, PhD, chief development officer at Viamet Pharmaceuticals, which is developing VT01161, presented the study findings during a late breaking clinical session at the meeting.

Adverse event rates and discontinuation rates were comparable to placebo through week 60, with no patients discontinuing due to any laboratory abnormalities. Nausea and muscle spasms were the most commonly reported adverse events, which Dr. Tavakkol said seemed to occur in patients given the higher doses. VT-1161 is also being studied for treatment of vulvovaginal candidiasis. In October 2016, the FDA granted the drug Qualified Infectious Disease Product and Fast Track designations for the treatment of recurrent vulvovaginal candidiasis, according to the company.

Viamet sponsored the study and Dr. Tavakkol is an employee of the company.

[email protected]

On Twitter @whitneymcknight

ORLANDO – A novel orally administered antifungal showed a favorable safety and efficacy profile in the treatment of distal lateral subungual onychomycosis, in a phase IIB study presented at the annual meeting of the American Academy of Dermatology.

In the RENOVATE (Restoring Nail: An Oral VT-1161 Tablet Evaluation) study, a randomized, double-blind, placebo-controlled, dose-ranging trial, 259 adults with moderate to severe distal lateral subungual onychomycosis of the large toenail were assigned to either one of four treatment arms. They were given the antifungal, currently named VT-1161, a selective CYP51 inhibitor, at doses of 300 mg or 600 mg once weekly for 10 or 22 weeks, after receiving daily loading doses for the initial 2 weeks. The trial evaluated two dose levels of VT-1161 (300 mg and 600 mg) administered once weekly for either 10 or 22 weeks following an initial 2-week, once-daily loading dose period.

At baseline, the average involvement of the large toenail was 46%, with an average of 4.6 toenails affected. In the intent-to-treat analysis, at 48 weeks, complete cure rates in the four study drug arms ranged from 32% to 42%, compared with 0% in the placebo arm.

Amir Tavakkol, PhD, chief development officer at Viamet Pharmaceuticals, which is developing VT01161, presented the study findings during a late breaking clinical session at the meeting.

Adverse event rates and discontinuation rates were comparable to placebo through week 60, with no patients discontinuing due to any laboratory abnormalities. Nausea and muscle spasms were the most commonly reported adverse events, which Dr. Tavakkol said seemed to occur in patients given the higher doses. VT-1161 is also being studied for treatment of vulvovaginal candidiasis. In October 2016, the FDA granted the drug Qualified Infectious Disease Product and Fast Track designations for the treatment of recurrent vulvovaginal candidiasis, according to the company.

Viamet sponsored the study and Dr. Tavakkol is an employee of the company.

[email protected]

On Twitter @whitneymcknight

To the Editor:
Vismodegib, a first-in-class inhibitor of the hedgehog signaling pathway, is useful in the treatment of advanced basal cell carcinomas (BCCs).¹ Common side effects of vismodegib include alopecia (58%), muscle spasms (71%), and dysgeusia (71%).² Some of these side effects have been hypothesized to be mechanism related.^3,4 Keratoacanthomas have been reported to occur after vismodegib treatment of BCC.⁵ We report 3 cases illustrating reversible cutaneous side effects of vismodegib: alopecia, follicular dermatitis, and drug hypersensitivity reaction.

A 53-year-old man with a locally advanced BCC of the right medial canthus began experiencing progressive and diffuse hair loss on the beard area, parietal scalp, eyelashes, and eyebrows after 2 months of vismodegib treatment. At 12 months of treatment, he had complete loss of eyelashes and eyebrows (Figure, A). After vismodegib was discontinued due to disease progression, all of his hair began regrowing within several months, with complete hair regrowth observed at 20 months after the last dose (Figure, B).

A 55-year-old man with several locally advanced BCCs developed new-onset mildly pruritic, acneform lesions on the chest and back after 4 months of vismodegib treatment. Biopsy of the lesions showed a folliculocentric mixed dermal infiltrate. The patient did not have a history of follicular dermatitis. The dermatitis resolved several months after onset without treatment, despite continued vismodegib.

A 55-year-old man with locally advanced BCCs developed erythematous dermal plaques on the arms and chest after 2 months of vismodegib treatment. Lesions were asymptomatic. He was not using any other medications and did not have any contact allergen exposures. Punch biopsy showed superficial and deep perivascular dermatitis with occasional eosinophils, consistent with drug hypersensitivity. Although lesions spontaneously resolved without treatment after 1 month, he experienced a couple more bouts of these lesions over the next year. He continued vismodegib for 2 years without return of this eruption.

The average time frame for hair regrowth after vismodegib cessation has not been characterized and awaits future larger studies. The frequency of follicular dermatitis and drug eruption also has not been determined and may require careful observation by dermatologists in larger numbers of treated patients. 

Because the hedgehog pathway is critical for normal hair follicle function, follicle-based toxicities of vismodegib including alopecia and folliculitis could be hypothesized to reflect effective blockade of the pathway.⁶ Currently, there are no data that these changes correlate with tumor response. 

Although alopecia is a recognized side effect of vismodegib, regrowth has not been previously reported.^1,2 Knowledge of the reversibility of alopecia as well as other toxicities has the potential to influence patient decision-making on drug initiation and adherence.

To the Editor:
Vismodegib, a first-in-class inhibitor of the hedgehog signaling pathway, is useful in the treatment of advanced basal cell carcinomas (BCCs).¹ Common side effects of vismodegib include alopecia (58%), muscle spasms (71%), and dysgeusia (71%).² Some of these side effects have been hypothesized to be mechanism related.^3,4 Keratoacanthomas have been reported to occur after vismodegib treatment of BCC.⁵ We report 3 cases illustrating reversible cutaneous side effects of vismodegib: alopecia, follicular dermatitis, and drug hypersensitivity reaction.

A 53-year-old man with a locally advanced BCC of the right medial canthus began experiencing progressive and diffuse hair loss on the beard area, parietal scalp, eyelashes, and eyebrows after 2 months of vismodegib treatment. At 12 months of treatment, he had complete loss of eyelashes and eyebrows (Figure, A). After vismodegib was discontinued due to disease progression, all of his hair began regrowing within several months, with complete hair regrowth observed at 20 months after the last dose (Figure, B).

A 55-year-old man with several locally advanced BCCs developed new-onset mildly pruritic, acneform lesions on the chest and back after 4 months of vismodegib treatment. Biopsy of the lesions showed a folliculocentric mixed dermal infiltrate. The patient did not have a history of follicular dermatitis. The dermatitis resolved several months after onset without treatment, despite continued vismodegib.

A 55-year-old man with locally advanced BCCs developed erythematous dermal plaques on the arms and chest after 2 months of vismodegib treatment. Lesions were asymptomatic. He was not using any other medications and did not have any contact allergen exposures. Punch biopsy showed superficial and deep perivascular dermatitis with occasional eosinophils, consistent with drug hypersensitivity. Although lesions spontaneously resolved without treatment after 1 month, he experienced a couple more bouts of these lesions over the next year. He continued vismodegib for 2 years without return of this eruption.

The average time frame for hair regrowth after vismodegib cessation has not been characterized and awaits future larger studies. The frequency of follicular dermatitis and drug eruption also has not been determined and may require careful observation by dermatologists in larger numbers of treated patients. 

Because the hedgehog pathway is critical for normal hair follicle function, follicle-based toxicities of vismodegib including alopecia and folliculitis could be hypothesized to reflect effective blockade of the pathway.⁶ Currently, there are no data that these changes correlate with tumor response. 

Although alopecia is a recognized side effect of vismodegib, regrowth has not been previously reported.^1,2 Knowledge of the reversibility of alopecia as well as other toxicities has the potential to influence patient decision-making on drug initiation and adherence.

To the Editor:
Vismodegib, a first-in-class inhibitor of the hedgehog signaling pathway, is useful in the treatment of advanced basal cell carcinomas (BCCs).¹ Common side effects of vismodegib include alopecia (58%), muscle spasms (71%), and dysgeusia (71%).² Some of these side effects have been hypothesized to be mechanism related.^3,4 Keratoacanthomas have been reported to occur after vismodegib treatment of BCC.⁵ We report 3 cases illustrating reversible cutaneous side effects of vismodegib: alopecia, follicular dermatitis, and drug hypersensitivity reaction.

A 53-year-old man with a locally advanced BCC of the right medial canthus began experiencing progressive and diffuse hair loss on the beard area, parietal scalp, eyelashes, and eyebrows after 2 months of vismodegib treatment. At 12 months of treatment, he had complete loss of eyelashes and eyebrows (Figure, A). After vismodegib was discontinued due to disease progression, all of his hair began regrowing within several months, with complete hair regrowth observed at 20 months after the last dose (Figure, B).

A 55-year-old man with several locally advanced BCCs developed new-onset mildly pruritic, acneform lesions on the chest and back after 4 months of vismodegib treatment. Biopsy of the lesions showed a folliculocentric mixed dermal infiltrate. The patient did not have a history of follicular dermatitis. The dermatitis resolved several months after onset without treatment, despite continued vismodegib.

A 55-year-old man with locally advanced BCCs developed erythematous dermal plaques on the arms and chest after 2 months of vismodegib treatment. Lesions were asymptomatic. He was not using any other medications and did not have any contact allergen exposures. Punch biopsy showed superficial and deep perivascular dermatitis with occasional eosinophils, consistent with drug hypersensitivity. Although lesions spontaneously resolved without treatment after 1 month, he experienced a couple more bouts of these lesions over the next year. He continued vismodegib for 2 years without return of this eruption.

The average time frame for hair regrowth after vismodegib cessation has not been characterized and awaits future larger studies. The frequency of follicular dermatitis and drug eruption also has not been determined and may require careful observation by dermatologists in larger numbers of treated patients. 

Because the hedgehog pathway is critical for normal hair follicle function, follicle-based toxicities of vismodegib including alopecia and folliculitis could be hypothesized to reflect effective blockade of the pathway.⁶ Currently, there are no data that these changes correlate with tumor response. 

Although alopecia is a recognized side effect of vismodegib, regrowth has not been previously reported.^1,2 Knowledge of the reversibility of alopecia as well as other toxicities has the potential to influence patient decision-making on drug initiation and adherence.

ORLANDO – The hair loss encounter – which can be challenging for both physicians and patients – should address the negative psychological effects of hair loss, including ways to camouflage hair loss, advised Adriana N. Schmidt, MD, a dermatologist in Santa Monica, Calif.

Dermatologists may spend so much time on the work-up – reviewing history regarding medication, lab values, and hair care practices – that they do not spend time to simply say to patients, “I want to help you feel better about yourself, and here’s how,” she said in a video interview at the annual meeting of the American Academy of Dermatology.

“What we can do is offer them a way to camouflage the hair loss,” Dr. Schmidt said. She shared tips that include creating a kit to keep in the office filled with lists of reputable hairpiece vendors and tattoo specialists in the community, as well as sample wigs, cosmetic powders, and other items to show to patients during hair loss consultations. She also offers thoughts on working with new hair styles and stylists to help improve the self-esteem of alopecia patients.

Dr. Schmidt had no relevant disclosures.

[email protected]
On Twitter @whitneymcknight

ORLANDO – The hair loss encounter – which can be challenging for both physicians and patients – should address the negative psychological effects of hair loss, including ways to camouflage hair loss, advised Adriana N. Schmidt, MD, a dermatologist in Santa Monica, Calif.

Dermatologists may spend so much time on the work-up – reviewing history regarding medication, lab values, and hair care practices – that they do not spend time to simply say to patients, “I want to help you feel better about yourself, and here’s how,” she said in a video interview at the annual meeting of the American Academy of Dermatology.

“What we can do is offer them a way to camouflage the hair loss,” Dr. Schmidt said. She shared tips that include creating a kit to keep in the office filled with lists of reputable hairpiece vendors and tattoo specialists in the community, as well as sample wigs, cosmetic powders, and other items to show to patients during hair loss consultations. She also offers thoughts on working with new hair styles and stylists to help improve the self-esteem of alopecia patients.

Dr. Schmidt had no relevant disclosures.

[email protected]
On Twitter @whitneymcknight

ORLANDO – The hair loss encounter – which can be challenging for both physicians and patients – should address the negative psychological effects of hair loss, including ways to camouflage hair loss, advised Adriana N. Schmidt, MD, a dermatologist in Santa Monica, Calif.

Dermatologists may spend so much time on the work-up – reviewing history regarding medication, lab values, and hair care practices – that they do not spend time to simply say to patients, “I want to help you feel better about yourself, and here’s how,” she said in a video interview at the annual meeting of the American Academy of Dermatology.

“What we can do is offer them a way to camouflage the hair loss,” Dr. Schmidt said. She shared tips that include creating a kit to keep in the office filled with lists of reputable hairpiece vendors and tattoo specialists in the community, as well as sample wigs, cosmetic powders, and other items to show to patients during hair loss consultations. She also offers thoughts on working with new hair styles and stylists to help improve the self-esteem of alopecia patients.

Dr. Schmidt had no relevant disclosures.

[email protected]
On Twitter @whitneymcknight

ORLANDO – Janus kinase inhibitors are “currently the most promising treatments” for alopecia areata, but they are expensive, are not approved for this indication, and so getting insurance coverage for these treatments can be difficult, Carolyn Goh, MD, said at the annual meeting of the American Academy of Dermatology.

In a video interview at the meeting, Dr. Goh of the department of dermatology, University of California, Los Angeles, shares the latest treatment algorithms that include these novel therapies, and thoughts on how to work with patients to increase their likelihood of getting insurance coverage for these treatments. Referring to the Janus kinase inhibitors, also known as JAK inhibitors, she said, “I think they would be very helpful for all patients with alopecia areata, but really given their side effect profile and risks involved, they should be reserved for more extensive disease.”

In the interview, Dr. Goh also discusses screening for thyroid disease in this patient population.

She had no disclosures.

[email protected]

On Twitter @whitneymcknight

ORLANDO – Janus kinase inhibitors are “currently the most promising treatments” for alopecia areata, but they are expensive, are not approved for this indication, and so getting insurance coverage for these treatments can be difficult, Carolyn Goh, MD, said at the annual meeting of the American Academy of Dermatology.

In a video interview at the meeting, Dr. Goh of the department of dermatology, University of California, Los Angeles, shares the latest treatment algorithms that include these novel therapies, and thoughts on how to work with patients to increase their likelihood of getting insurance coverage for these treatments. Referring to the Janus kinase inhibitors, also known as JAK inhibitors, she said, “I think they would be very helpful for all patients with alopecia areata, but really given their side effect profile and risks involved, they should be reserved for more extensive disease.”

In the interview, Dr. Goh also discusses screening for thyroid disease in this patient population.

She had no disclosures.

[email protected]

On Twitter @whitneymcknight

ORLANDO – Janus kinase inhibitors are “currently the most promising treatments” for alopecia areata, but they are expensive, are not approved for this indication, and so getting insurance coverage for these treatments can be difficult, Carolyn Goh, MD, said at the annual meeting of the American Academy of Dermatology.

In a video interview at the meeting, Dr. Goh of the department of dermatology, University of California, Los Angeles, shares the latest treatment algorithms that include these novel therapies, and thoughts on how to work with patients to increase their likelihood of getting insurance coverage for these treatments. Referring to the Janus kinase inhibitors, also known as JAK inhibitors, she said, “I think they would be very helpful for all patients with alopecia areata, but really given their side effect profile and risks involved, they should be reserved for more extensive disease.”

In the interview, Dr. Goh also discusses screening for thyroid disease in this patient population.

She had no disclosures.

[email protected]

On Twitter @whitneymcknight

ORLANDO – Two hair loss clinical grading tools can help physicians and their female androgenetic alopecia patients set medical treatment expectations, and make tracking progress both easier and more accurate, according to the dermatologist who developed the scales.

The five-point clinical grading scale helps physicians with diagnosing female pattern hair loss and grading the severity, Rodney Sinclair, MD, said in a video interview at the annual meeting of the American Academy of Dermatology. “And you can use that clinical grading scale to monitor the response to treatment” and show patients what to expect with treatment, added Dr. Sinclair, professor and chairman, department of dermatology, Epworth Hospital, Melbourne.

He also discussed a validated hair shedding scale, “a really simple and easy test to use,” with six photographs to help patients determine how much hair they are shedding on a daily basis. “Most women don’t know what’s a normal amount of hair to shed,” he said. In the interview, Dr. Sinclair explains more about the two scales, and how they can be used to obtain clinically relevant information to help guide treatment – and shares his tips for how to work with women who are anxious about their hair loss improvement.

Dr. Sinclair owns the copyrights for the Sinclair Severity Scale. He has no other relevant disclosures.

[email protected]
On Twitter @whitneymcknight

ORLANDO – Two hair loss clinical grading tools can help physicians and their female androgenetic alopecia patients set medical treatment expectations, and make tracking progress both easier and more accurate, according to the dermatologist who developed the scales.

The five-point clinical grading scale helps physicians with diagnosing female pattern hair loss and grading the severity, Rodney Sinclair, MD, said in a video interview at the annual meeting of the American Academy of Dermatology. “And you can use that clinical grading scale to monitor the response to treatment” and show patients what to expect with treatment, added Dr. Sinclair, professor and chairman, department of dermatology, Epworth Hospital, Melbourne.

He also discussed a validated hair shedding scale, “a really simple and easy test to use,” with six photographs to help patients determine how much hair they are shedding on a daily basis. “Most women don’t know what’s a normal amount of hair to shed,” he said. In the interview, Dr. Sinclair explains more about the two scales, and how they can be used to obtain clinically relevant information to help guide treatment – and shares his tips for how to work with women who are anxious about their hair loss improvement.

Dr. Sinclair owns the copyrights for the Sinclair Severity Scale. He has no other relevant disclosures.

[email protected]
On Twitter @whitneymcknight

ORLANDO – Two hair loss clinical grading tools can help physicians and their female androgenetic alopecia patients set medical treatment expectations, and make tracking progress both easier and more accurate, according to the dermatologist who developed the scales.

The five-point clinical grading scale helps physicians with diagnosing female pattern hair loss and grading the severity, Rodney Sinclair, MD, said in a video interview at the annual meeting of the American Academy of Dermatology. “And you can use that clinical grading scale to monitor the response to treatment” and show patients what to expect with treatment, added Dr. Sinclair, professor and chairman, department of dermatology, Epworth Hospital, Melbourne.

He also discussed a validated hair shedding scale, “a really simple and easy test to use,” with six photographs to help patients determine how much hair they are shedding on a daily basis. “Most women don’t know what’s a normal amount of hair to shed,” he said. In the interview, Dr. Sinclair explains more about the two scales, and how they can be used to obtain clinically relevant information to help guide treatment – and shares his tips for how to work with women who are anxious about their hair loss improvement.

Dr. Sinclair owns the copyrights for the Sinclair Severity Scale. He has no other relevant disclosures.

[email protected]
On Twitter @whitneymcknight

Lupus erythematosus tumidus (LET) is a relatively rare condition but may simply be underdiagnosed in the literature. It presents as urticarialike papules and plaques in sun-exposed areas, characterized by induration and erythema. Lesions occur on the face, neck, upper extremities, and trunk and heal without scarring.^1,2 Rarely, lesions can show fine scaling and associated pruritus, but most often the lesions are asymptomatic.³

Case Report

A 45-year-old woman presented with 2 asymptomatic self-described bald spots on the top of the head of 2 months’ duration. The patient denied prior treatment of the lesions and noted one patch was resolving. She reported no involvement of the eyebrows, eyelashes, and axillary and pubic hair. A review of systems was negative. The patient denied personal or family history of lupus, thyroid disease, or vitiligo.

Clinical examination revealed a 1.1-cm round patch of nonscarring alopecia on the right vertex scalp and a 0.9-cm round patch of nonscarring alopecia with moderate hair regrowth on the left vertex scalp. There was no erythema, scaling, or induration. The rest of the scalp was normal in appearance and the eyebrows and eyelashes were uninvolved. The patient was diagnosed with alopecia areata and was treated with 10 mg/mL of intralesional triamcinolone once monthly for 4 months.

The patient initially showed improvement with moderate hair regrowth. After 4 months of treatment, she developed 3 new 1- to 1.5-cm erythematous alopecic patches on the vertex scalp and had worsening in the initial patches (Figure 1). Given the resistance to standard therapy and the onset of multiple new areas with evidence of inflammatory involvement, a punch biopsy was performed. Histopathologic examination revealed a fairly unremarkable epidermis and a dense dermal inflammatory infiltrate that was present both in the superficial and deep dermis (Figure 2). The inflammatory cells, which appeared to be predominantly comprised of lymphocytes, had a predilection for the vasculature but also were observed within the interstitial dermis. Additionally, mucin appeared to be slightly increased in the deep dermis. The lymphocytic phenotype was confirmed by immunohistochemical studies for CD20 and CD3. The most likely possibilities for this reaction pattern were LET, Jessner lymphocytic infiltrate of the skin (JLIS), gyrate erythema, and lymphoma; however, the immunohistochemical studies effectively ruled out lymphoma. Additionally, there was pronounced dermal mucin noted in the specimen. The patient was diagnosed with LET of the scalp based on the constellation of findings.

Comment

The classification of LET as a single unique entity or disease process sui generis has been in flux in the last decade. Its similarities to JLIS and other forms of chronic cutaneous lupus erythematosus (CCLE) have brought debate.^4-6 In 1930, Gougerot and Burnier⁷ documented the first case of LET in the literature, describing smooth, infiltrated, erythematous lesions with no desquamation or other superficial changes seen in 5 patients.

In 2000, interest in LET and other forms of CCLE was increasing, and reports in the literature paralleled. That year, Kuhn et al⁴ reported 40 cases of LET, characterizing the clinical and histological features of each case to demonstrate that LET should be separate from other forms of CCLE. Until then, it is likely that many lesions that should have been classified as LET were instead classified as various forms of CCLE. The investigators maintained that LET also should be distinct from JLIS because it is associated with UV exposure.⁴ Kuhn et al⁸ reviewed phototesting in 60 patients with LET in 2001 and confirmed this subset was the most photosensitive type of lupus erythematosus.

In general, the histopathologic and immunohistochemical studies in LET and JLIS can be quite similar. Relatively distinguishing histopathologic findings in JLIS include no evidence of epidermal atrophy, basal vacuolar change, or follicular plugging, as well as negative immunofluorescence studies. Both entities show a predominantly T-cell population with a smaller component of B cells and thus a distinction cannot be made based on relative proportions of T and B cells in lesions.²

In 2003, Alexiades-Armenakas et al⁶ determined immunohistochemical criteria for LET, finding a predominance of T cells and more CD4 lymphocytes than CD8 lymphocytes with a mean ratio of roughly 3 to 1. Their study results maintained LET should be classified as a form of CCLE due to the chronicity of the lesions, the serologic profile with negative anti–double-stranded DNA, anticentromere, anti-Smith, anti-Ro/Sjögren syndrome antigen A, anti-La/Sjögren syndrome antigen B, and anti-nuclear ribonucleoprotein antibodies and the rare association with systemic disease.⁶ This conclusion was further solidified by a review published that same year citing unique histopathological features when compared to subacute cutaneous LE and discoid lupus erythematosus.⁵

This case illustrates the importance of histologic evaluation in determining the correct diagnosis in a patient with alopecia areata recalcitrant to treatment. Including LET in the differential of alopecic patches on the scalp could prove beneficial for patients, as LET responds well to antimalarial drugs and photoprotection.⁹ This patient had a normal antinuclear antibody panel and no signs or symptoms of systemic lupus. It was recommended that she avoid sun exposure and begin treatment with hydroxychloroquine but she declined. At a follow-up visit 6 months later she reported the lesions had improved, but a permanent wig had been sewn over the area, so it could not be examined.

Lupus erythematosus tumidus (LET) is a relatively rare condition but may simply be underdiagnosed in the literature. It presents as urticarialike papules and plaques in sun-exposed areas, characterized by induration and erythema. Lesions occur on the face, neck, upper extremities, and trunk and heal without scarring.^1,2 Rarely, lesions can show fine scaling and associated pruritus, but most often the lesions are asymptomatic.³

Case Report

A 45-year-old woman presented with 2 asymptomatic self-described bald spots on the top of the head of 2 months’ duration. The patient denied prior treatment of the lesions and noted one patch was resolving. She reported no involvement of the eyebrows, eyelashes, and axillary and pubic hair. A review of systems was negative. The patient denied personal or family history of lupus, thyroid disease, or vitiligo.

Clinical examination revealed a 1.1-cm round patch of nonscarring alopecia on the right vertex scalp and a 0.9-cm round patch of nonscarring alopecia with moderate hair regrowth on the left vertex scalp. There was no erythema, scaling, or induration. The rest of the scalp was normal in appearance and the eyebrows and eyelashes were uninvolved. The patient was diagnosed with alopecia areata and was treated with 10 mg/mL of intralesional triamcinolone once monthly for 4 months.

The patient initially showed improvement with moderate hair regrowth. After 4 months of treatment, she developed 3 new 1- to 1.5-cm erythematous alopecic patches on the vertex scalp and had worsening in the initial patches (Figure 1). Given the resistance to standard therapy and the onset of multiple new areas with evidence of inflammatory involvement, a punch biopsy was performed. Histopathologic examination revealed a fairly unremarkable epidermis and a dense dermal inflammatory infiltrate that was present both in the superficial and deep dermis (Figure 2). The inflammatory cells, which appeared to be predominantly comprised of lymphocytes, had a predilection for the vasculature but also were observed within the interstitial dermis. Additionally, mucin appeared to be slightly increased in the deep dermis. The lymphocytic phenotype was confirmed by immunohistochemical studies for CD20 and CD3. The most likely possibilities for this reaction pattern were LET, Jessner lymphocytic infiltrate of the skin (JLIS), gyrate erythema, and lymphoma; however, the immunohistochemical studies effectively ruled out lymphoma. Additionally, there was pronounced dermal mucin noted in the specimen. The patient was diagnosed with LET of the scalp based on the constellation of findings.

Comment

The classification of LET as a single unique entity or disease process sui generis has been in flux in the last decade. Its similarities to JLIS and other forms of chronic cutaneous lupus erythematosus (CCLE) have brought debate.^4-6 In 1930, Gougerot and Burnier⁷ documented the first case of LET in the literature, describing smooth, infiltrated, erythematous lesions with no desquamation or other superficial changes seen in 5 patients.

In 2000, interest in LET and other forms of CCLE was increasing, and reports in the literature paralleled. That year, Kuhn et al⁴ reported 40 cases of LET, characterizing the clinical and histological features of each case to demonstrate that LET should be separate from other forms of CCLE. Until then, it is likely that many lesions that should have been classified as LET were instead classified as various forms of CCLE. The investigators maintained that LET also should be distinct from JLIS because it is associated with UV exposure.⁴ Kuhn et al⁸ reviewed phototesting in 60 patients with LET in 2001 and confirmed this subset was the most photosensitive type of lupus erythematosus.

In general, the histopathologic and immunohistochemical studies in LET and JLIS can be quite similar. Relatively distinguishing histopathologic findings in JLIS include no evidence of epidermal atrophy, basal vacuolar change, or follicular plugging, as well as negative immunofluorescence studies. Both entities show a predominantly T-cell population with a smaller component of B cells and thus a distinction cannot be made based on relative proportions of T and B cells in lesions.²

In 2003, Alexiades-Armenakas et al⁶ determined immunohistochemical criteria for LET, finding a predominance of T cells and more CD4 lymphocytes than CD8 lymphocytes with a mean ratio of roughly 3 to 1. Their study results maintained LET should be classified as a form of CCLE due to the chronicity of the lesions, the serologic profile with negative anti–double-stranded DNA, anticentromere, anti-Smith, anti-Ro/Sjögren syndrome antigen A, anti-La/Sjögren syndrome antigen B, and anti-nuclear ribonucleoprotein antibodies and the rare association with systemic disease.⁶ This conclusion was further solidified by a review published that same year citing unique histopathological features when compared to subacute cutaneous LE and discoid lupus erythematosus.⁵

This case illustrates the importance of histologic evaluation in determining the correct diagnosis in a patient with alopecia areata recalcitrant to treatment. Including LET in the differential of alopecic patches on the scalp could prove beneficial for patients, as LET responds well to antimalarial drugs and photoprotection.⁹ This patient had a normal antinuclear antibody panel and no signs or symptoms of systemic lupus. It was recommended that she avoid sun exposure and begin treatment with hydroxychloroquine but she declined. At a follow-up visit 6 months later she reported the lesions had improved, but a permanent wig had been sewn over the area, so it could not be examined.

Lupus erythematosus tumidus (LET) is a relatively rare condition but may simply be underdiagnosed in the literature. It presents as urticarialike papules and plaques in sun-exposed areas, characterized by induration and erythema. Lesions occur on the face, neck, upper extremities, and trunk and heal without scarring.^1,2 Rarely, lesions can show fine scaling and associated pruritus, but most often the lesions are asymptomatic.³

Case Report

A 45-year-old woman presented with 2 asymptomatic self-described bald spots on the top of the head of 2 months’ duration. The patient denied prior treatment of the lesions and noted one patch was resolving. She reported no involvement of the eyebrows, eyelashes, and axillary and pubic hair. A review of systems was negative. The patient denied personal or family history of lupus, thyroid disease, or vitiligo.

Clinical examination revealed a 1.1-cm round patch of nonscarring alopecia on the right vertex scalp and a 0.9-cm round patch of nonscarring alopecia with moderate hair regrowth on the left vertex scalp. There was no erythema, scaling, or induration. The rest of the scalp was normal in appearance and the eyebrows and eyelashes were uninvolved. The patient was diagnosed with alopecia areata and was treated with 10 mg/mL of intralesional triamcinolone once monthly for 4 months.

The patient initially showed improvement with moderate hair regrowth. After 4 months of treatment, she developed 3 new 1- to 1.5-cm erythematous alopecic patches on the vertex scalp and had worsening in the initial patches (Figure 1). Given the resistance to standard therapy and the onset of multiple new areas with evidence of inflammatory involvement, a punch biopsy was performed. Histopathologic examination revealed a fairly unremarkable epidermis and a dense dermal inflammatory infiltrate that was present both in the superficial and deep dermis (Figure 2). The inflammatory cells, which appeared to be predominantly comprised of lymphocytes, had a predilection for the vasculature but also were observed within the interstitial dermis. Additionally, mucin appeared to be slightly increased in the deep dermis. The lymphocytic phenotype was confirmed by immunohistochemical studies for CD20 and CD3. The most likely possibilities for this reaction pattern were LET, Jessner lymphocytic infiltrate of the skin (JLIS), gyrate erythema, and lymphoma; however, the immunohistochemical studies effectively ruled out lymphoma. Additionally, there was pronounced dermal mucin noted in the specimen. The patient was diagnosed with LET of the scalp based on the constellation of findings.

Comment

The classification of LET as a single unique entity or disease process sui generis has been in flux in the last decade. Its similarities to JLIS and other forms of chronic cutaneous lupus erythematosus (CCLE) have brought debate.^4-6 In 1930, Gougerot and Burnier⁷ documented the first case of LET in the literature, describing smooth, infiltrated, erythematous lesions with no desquamation or other superficial changes seen in 5 patients.

In 2000, interest in LET and other forms of CCLE was increasing, and reports in the literature paralleled. That year, Kuhn et al⁴ reported 40 cases of LET, characterizing the clinical and histological features of each case to demonstrate that LET should be separate from other forms of CCLE. Until then, it is likely that many lesions that should have been classified as LET were instead classified as various forms of CCLE. The investigators maintained that LET also should be distinct from JLIS because it is associated with UV exposure.⁴ Kuhn et al⁸ reviewed phototesting in 60 patients with LET in 2001 and confirmed this subset was the most photosensitive type of lupus erythematosus.

In general, the histopathologic and immunohistochemical studies in LET and JLIS can be quite similar. Relatively distinguishing histopathologic findings in JLIS include no evidence of epidermal atrophy, basal vacuolar change, or follicular plugging, as well as negative immunofluorescence studies. Both entities show a predominantly T-cell population with a smaller component of B cells and thus a distinction cannot be made based on relative proportions of T and B cells in lesions.²

In 2003, Alexiades-Armenakas et al⁶ determined immunohistochemical criteria for LET, finding a predominance of T cells and more CD4 lymphocytes than CD8 lymphocytes with a mean ratio of roughly 3 to 1. Their study results maintained LET should be classified as a form of CCLE due to the chronicity of the lesions, the serologic profile with negative anti–double-stranded DNA, anticentromere, anti-Smith, anti-Ro/Sjögren syndrome antigen A, anti-La/Sjögren syndrome antigen B, and anti-nuclear ribonucleoprotein antibodies and the rare association with systemic disease.⁶ This conclusion was further solidified by a review published that same year citing unique histopathological features when compared to subacute cutaneous LE and discoid lupus erythematosus.⁵

This case illustrates the importance of histologic evaluation in determining the correct diagnosis in a patient with alopecia areata recalcitrant to treatment. Including LET in the differential of alopecic patches on the scalp could prove beneficial for patients, as LET responds well to antimalarial drugs and photoprotection.⁹ This patient had a normal antinuclear antibody panel and no signs or symptoms of systemic lupus. It was recommended that she avoid sun exposure and begin treatment with hydroxychloroquine but she declined. At a follow-up visit 6 months later she reported the lesions had improved, but a permanent wig had been sewn over the area, so it could not be examined.